jrnls.org logo
Submit

BROWSE ALL JOURNALS

SEE ALL 19 JOURNALS
International Journal of Pharmaceutical InvestigationNOW IN
Review

An Overview on Microneedle Technology: Superior Pharmaceutical Transdermal Delivery Forms

Paramita Ganguly1, Puja Saha2, Sourav Khawas3, Sandip Chatterjee4★, Arvind Kumar Patel5, Prangyan Paramita Pati6★ Corresponding author

  1. 1Department of Pharmaceutical Technology, Brainware University, Barasat, Kolkata, West Bengal, INDIA.
  2. 2Department of Pharmaceutics, Mata Gujri College of Pharmacy, Mata Gujri University, Purab Palli Road, Kishanganj, Bihar, INDIA.
  3. 3Department of Pharmacy, Jharkhand Rai University, Raja Ullatu, Ranchi, Jharkhand, INDIA.
  4. 4Department of Pharmacognosy, Narayan institute of Pharmacy, Gopal Narayan Singh University, Sasaram, Rohtas, INDIA.
  5. 5Department of Pharmacology, Narayan institute of Pharmacy, Gopal Narayan Singh University, Sasaram, Rohtas, India.
  6. 6Department of Pharmacognosy, Gayatri College of Pharmacy, Sambalpur, Odisha, INDIA.

CORRESPONDENCE

Sandip Chatterjee

Assistant Professor at Narayan Institute of Pharmacy, Gopal Narayan Singh University, Jamuhar, Sasaram-821305, Bihar, INDIA.

sandipkarna1994@gmail.com

ORCID: 0009-0005-9043-3364

Received: 07-04-2025; Revised: 26-06-2025; Accepted: 18-08-2025.

Volume 16, Issue 1 · pp. 77–88 · PUBLISHED Jan-Mar 2026 · DOI: 10.5530/ijpi.20260499

View on IJPI original site ↗

ABSTRACT

Microneedles, first introduced in 1976, address these limitations by creating tiny, non-invasive channels that enhance drug penetration through the skin. Transdermal Drug Delivery (TDD) is a less intrusive approach that bypasses first-pass metabolism and enables self-administration. However, the Stratum corneum, the skin’s outermost layer, acts as a strong barrier, restricting drug absorption. While hypodermic needle injections are effective, they are invasive, painful, and produce hazardous waste. Moreover, they are less efficient for vaccine delivery, as they administer the drug into muscle rather than the skin. Microneedles have proven effective in enhancing the delivery of various drugs, including vaccines and protein therapeutics, and can be designed with different materials and structures to maximize performance. The success of pharmaceuticals depends not only on the drug itself but also on the delivery method. While oral administration is convenient, it presents challenges for certain drugs due to low absorption or degradation. Microneedles provide an innovative alternative, enabling the efficient delivery of both small molecules and large proteins with minimal pain and high bioavailability. As a breakthrough in drug delivery technology, they offer a promising solution to the limitations of traditional methods.

KEYWORDS

0% READ

FULL TEXT

INTRODUCTION

Microneedles are a revolutionary advancement in drug delivery, featuring ultra-small needles that minimally penetrate the skin while bypassing the stratum corneum-the primary barrier that restricts absorption. This innovative design enhances drug uptake and effectively eliminates the first-pass metabolism, significantly improving delivery efficiency (Tibbitt et al., 2016). There is improvement in the efficacy of the medication and possibly the loss of pain and what is commonly referred to as the invasiveness of injections (Engelke et al., 2015). Material selection is crucial in microneedle design, as it directly impacts performance. Polymer-based systems have gained significant attention for microneedle fabrication due to their biocompatibility and biodegradability within the body. This versatility allows microneedles to be tailored to specific drug types and delivery requirements, enhancing their effectiveness (Prausnitz and Langer, 2008; Choy and Prausnitz, 2011).

Microneedles (MN) have emerged as a highly promising drug delivery system, capable of efficiently administering a wide range of substances, including vaccines, insulin, growth hormones, and oligonucleotides (Kim et al., 2012). Their ability to penetrate tissue with minimal damage makes microneedles ideal for delicate applications such as ocular drug delivery and gene transfer. However, despite their promise, further research and development are necessary to fully optimize their potential (Boehm et al., 2012). The delivery of large molecules, such as proteins, remains a challenge due to their size, hydrophilicity, and potential instability. However, continuous research and technological advancements are making significant progress in overcoming these obstacles (Bhatnagar et al., 2017). Microneedles represent a groundbreaking innovation in drug delivery technology. With their ability to administer drugs painlessly, efficiently, and minimally invasively, they offer a compelling alternative to traditional methods. As advancements in material science continue, their role in drug therapy is expected to expand significantly (Amorij et al., 2010).

Needs of microneedles aspects from other dosages form

Significantly less painful than traditional injections, microneedles offer a nearly pain-free alternative. Research also suggests that children are more willing to have their blood drawn using microneedles, as they cause considerably less discomfort than conventional needles (Traverso et al., 2015). The likelihood of greater compliance with medical therapies and improved patient experience are also probable advantages with lesser pain from this invention. They are also smaller; thus, less chance of tissue damage, making them safer for certain uses (Lhernould et al., 2015). Microneedles also benefit physicians by generating less hazardous waste and offering greater ease of handling, making them a safer and more efficient alternative to traditional needles (Kochhar et al., 2019). Microneedles are more cost-effective than traditional needles, requiring less material and being manufactured from more affordable substances (Ma and Wu, 2017). Microneedles are less painful, cause less waste, and provide a safer, more convenient at-home administration alternative to conventional needles. A potential disadvantage is the risk of unintentional needle-stick injury (Figure 1) (Donnelly and Douroumis, 2015). Microneedles significantly reduce the risk of infection at the puncture site following vaccine or drug administration (Lee et al., 2010). Unlike traditional needles, which create larger wounds that can become infected over time, allowing bacteria to enter the bloodstream, microneedles cause much smaller, shallower punctures that heal significantly faster, reducing the risk of infection. However, further research is needed to determine whether certain bacteria can still penetrate these relatively shallow wounds (Xiang et al., 2014).

Figure 1: Mechanism efficacy microneedle under skin superior drug delivery technology.

Limitation of microneedles

Actually, correct use of microneedles helps in the proper delivery of a full dose of medication or vaccine (Jiang et al., 2009). If applied incorrectly or damaged, microneedles may cause the drug to leak onto the skin rather than penetrate the body effectively. Therefore, proper training for healthcare providers is essential to ensure correct application and maximize the drug's efficacy (Dharadhar et al., 2019). Microneedles are typically much softer than conventional needles. However, there is a risk of tiny fragments breaking off and remaining in the skin, potentially causing irritation or other complications. Therefore, they should be used with caution (Prausnitz et al., 2017). The available literature on drug delivery through microneedles is limited, as current research primarily focuses on developing practical microneedles and optimizing their design and application (Ye et al., 2018).

Classifications of Microneedles

Categorized by material

The MNs can be fabricated using a host of materials: silicon, glass, ceramics, metals, hydrogels, polymers, and sugar (McAllister et al., 2000; Bediz et al., 2014). Silicon was the preferred material for early generations of microneedles due to its rigidity and ease of penetration. However, its high cost and susceptibility to breakage rendered it impractical for widespread use (McConville et al., 2018). Metals like stainless steel, titanium, nickel, and palladium have good mechanical properties and can be produced cost-effectively by methods such as electroplating, photochemical etching, micro-milling, and laser cutting. But because of safety issues, stainless steel and titanium are the only metals that are viable for use in medicine. Metal microneedles also produce biohazardous waste, which has to be disposed of in a responsible manner (Jeong et al., 2017).

The selection of microneedle materials varies based on the optimal balance of cost, performance, and safety for specific applications. While silicon offers advantages such as rigidity and ease of penetration, its drawbacks often outweigh these benefits in certain implementations (Coulman et al., 2006). Metals offer superior mechanical properties and cost-effectiveness; however, their safety and environmental impact must be carefully considered (Cormier et al., 2004). Material selection significantly influences the biocompatibility of microneedles with the skin, as certain materials may trigger immune responses or cause irritation. Additionally, penetration efficiency depends on surface properties such as roughness and coating, which further impact the release of active substances (Rzhevskiy et al., 2018; Daddona et al., 2011).

Categorized by structures of Microneedles

From a structural perspective, microneedles can be categorized as either in-plane or out-of-plane. In in-plane microneedles, the needle length runs parallel to the substrate surface, whereas in out-of-plane microneedles, the longitudinal axis is perpendicular to the substrate (Thakur et al., 2016). From a fabrication perspective, array densities of out-of-plane MNs are generally relatively high and this could increase drug delivery efficiency. Long out-of-plane MNs, for instance, through etching or molding, are theoretically possible, but such configurations raise some issues (Martanto et al., 2006).

In the initial stage, in-plane microneedles were fabricated using inclined ultraviolet lithography and electroforming. Subsequently, these in-plane microneedles were assembled layer by layer into an out-of-plane microneedle array (Badran et al., 2009). A polycarbonate out-of-plane microneedle array was generated by hot embossing in a machine with the negative Mold after a duplication process produced a negative Mold of the microneedle array (Banga, 2009).

Categorized by drug transportation method

While the design of microneedles varies based on the route of administration, type, and mechanism of action, most patches share common fundamental characteristics (Yan et al., 2010). A typical microneedle measures between 150 and 1500 μm in length, 50 to 250 μm in width, and has a tapered, sharp-pointed tip with a thickness ranging from 1 to 25 μm (Oh et al., 2008). The drug is typically either coated onto or encapsulated within the microneedle tip, which is then mounted on a base substrate to form an array (Waghule et al., 2019). This array is then placed onto a patch backing for convenience, and the backing will typically feature a skin adhesive to ensure good contact with the skin (Haj-Ahmad et al., 2015). Microneedles are typically categorized into five types:

  • Solid
  • Hollow
  • Coated
  • Dissolvable
  • Hydrogel-forming

Solid Microneedles

These needles, made from a single material such as silicon or stainless steel, are designed to puncture the skin and create microchannels for drug delivery (Jiang et al., 2007). This approach significantly enhances drug absorption by bypassing the stratum corneum, the outermost skin layer, and directly accessing the underlying capillaries (Gill and Prausnitz, 2007).

Hollow microneedles

Hollow-core microneedles can be filled with a liquid drug solution, with the hollow opening serving as a channel for drug release into the skin. While this technique enables direct drug delivery, it may encounter challenges such as clogging or buckling, which can disrupt the administration process (Shakya et al., 2019).

Coated microneedles

The surface of such needles is drug-coated and usually made of some water-soluble polymer or other biodegradable material (Sullivan et al., 2010). As the microneedle dissolves or degrades upon contact with the skin, the drug is gradually released, enabling controlled and sustained drug delivery while minimizing systemic side effects (Edens et al., 2015).

Dissolvable microneedles

Dissolvable microneedles are made from biodegradable or water-soluble materials that break down upon contact with the skin, eliminating the need for special sharps disposal (Hirobe et al., 2015). This approach is highly beneficial as it minimizes the risk of accidental needle-stick injuries and associated infections. Common materials used for dissolvable microneedles include carboxymethyl cellulose, methyl cellulose, and various saccharides (Quinn et al., 2015).

Hydrogel microneedles

The hydrogel matrix contains the drug embedded in the needles. In that way, the hydrogel expands upon contacting the skin and slowly delivers the drug afterwards (Mistilis et al., 2015). This method is particularly suitable for drugs intended for prolonged retention in the skin, such as growth factors and hormone injections. Hydrogel microneedles can be engineered to enable controlled drug release, ensuring optimal therapeutic outcomes (Raphael et al., 2016).

Material for microneedles

A key advantage of microneedles is their resistance to bending or breaking upon skin penetration. Overcoming manufacturing challenges requires careful selection of materials, production techniques, and design. A wide range of materials, including silicon, metals, ceramics, and polymers, has been utilized to develop various types of microneedles (Al Sulaiman et al., 2019).

Silicon

Silicon was first used to create microneedles in the 1990s, offering two key advantages, its flexibility enables the fabrication of a wide range of shapes and sizes, and it is suitable for manufacturing solid, hollow, and coated microneedles. However, silicon also has notable drawbacks, including a lengthy fabrication process, high production costs, and the risk of breakage within the skin during application (He et al., 2020).

Metal

Metals have been widely utilized in microneedle production due to their biocompatibility and outstanding mechanical properties, including high fracture toughness and superior yield strength. These attributes make metal-based microneedles more durable and less prone to breakage compared to their silicon counterparts (Yu et al., 2015). Stainless steel and titanium are the two primary metals evaluated for microneedle fabrication. While metal microneedles effectively penetrate the skin, they may occasionally trigger allergic reactions (Zhao et al., 2018).

Ceramic

Ceramic materials such as alumina are employed during MN preparation because of their high chemical stability and compressive resistance. Tensile strength in the case of alumina is considerably less compared to other materials (Desai et al., 2021). Other ceramics, such as calcium sulfate dihydrate and calcium phosphate dihydrate, have been utilized in microneedle fabrication. The micro-molding technique plays a crucial role in the large-scale production of ceramic microneedles, offering a cost-effective manufacturing solution (Yang et al., 2013).

Polymer

Polymer-based microneedle arrays show great potential for drug delivery applications due to their biocompatibility, low toxicity, and cost-effectiveness. However, they are generally less durable than those made from silicon or metals (Martanto et al., 2004). Polymers are the most commonly used materials for manufacturing dissolvable, hydrogel-forming, solid, coated, and hollow microneedle arrays (Harvey et al., 2011). Various drugs have been successfully delivered using microneedle arrays made from biodegradable polymers. Some of the most commonly used polymers for microneedle fabrication include poly (methyl methacrylate) (PMMA), Polylactic Acid (PLA), polycarbonate, polystyrene, and SU-8 photoresist (Marquetti and Desai, 2019).

Manufacturing methods for microneedles

Lithography

The lithography process used in microneedle fabrication is known as lithography. In this technique, a photoresist, a light-sensitive material is utilized to capture intricate patterns on surfaces. These patterns are then transferred onto the substrate through subsequent chemical etching (McAllister et al., 2003). Although lithography offers superior resolution and flexibility, it has certain limitations. The process demands a highly controlled cleanroom environment to prevent sample contamination and ensure the precise replication of patterns (Kendall et al., 2007). Furthermore, it is a slow process involving several sequential operations, including photolithographic application of the resist, exposure, development, and etching. All these elements bring out the comparatively high price it has in producing products in large quantities (Cormier et al., 2004). Despite these limitations, lithography remains one of the most important techniques for manufacturing complex geometrical and high-precision microneedles (Sharma, 2018). Indeed, lithography enables the fabrication of microneedles using a wide range of materials, including glass, metal, ceramics, and plastics. By meticulously controlling the lithography process, researchers can achieve microneedles with precisely tailored dimensions, shapes, and surface characteristics (Larrañeta et al., 2016).

Laser Ablation

Laser ablation is a highly promising technique for precise material removal and has also emerged as an advanced method for fabricating microneedle arrays. This process relies on a focused laser beam to ablate material from a substrate, creating intricate patterns and well-defined structures (Ma et al., 2014). Different laser types, including carbon di oxide, ultra violet excimer, and femtosecond lasers, have been used to create microneedles (O’Mahony, 2014). The use of a high-energy laser beam enables exceptional removal speed and precision within nanoseconds, completely ablating the material. This rapid and precise process is ideal for fabricating microneedles with intricate geometries and precisely controlled dimensions (Niinomi and Nakai, 2011). Although laser ablation has numerous advantages, the ablation point is still attached to thermal effects. Thus, such thermal effects might influence the microneedle structure and therefore the mechanical properties, leading to undesirable effects like cracking or reduced fatigue strength. Optimal adjustment of the laser parameters utilized as well as proper material choice is thus necessary (Monteiro-Riviere, 2010).

Despite the drawbacks of thermal effects, laser ablation remains a highly viable technique for microneedle fabrication. Its versatility, speed, and precision make it invaluable for various applications, including drug delivery, diagnostic testing, and cosmetic procedures. However, the process often requires significant initial investment in laser equipment and may pose challenges for large-scale manufacturing (Ita, 2015; Verbaan et al., 2007).

Micro-Molding

One highly precise and cost-effective manufacturing technique for mass-producing microneedles is both scalable and efficient. This method typically involves creating a master mold, followed by casting with a suitable polymer material containing active pharmaceutical ingredients. As a result, it enables the fabrication of an exceptionally high volume of microneedles with outstanding precision and uniformity (Aldawood et al., 2021). The work material, Polydimethylsiloxane (PDMS), is characterized by having excellent features of low price, easy hand ability, low surface energy, and high thermal stability. The unique features favour the use of PDMS as an excellent option to create elaborate microneedle structures of definite geometries with well-distinguishable surface properties (Indermun et al., 2014). As with any process, however, advantages may go hand-in-hand with other challenges that must be overcome before it could successfully realize the desired output (Bystrova and Luttge, 2011). For instance, the penetration depth and drug load capacity of microneedles significantly impact the overall safety and effectiveness of drug delivery. By leveraging micro-molding, researchers can produce high-quality microneedles for medical applications, ensuring precise control over these critical factors through well-implemented regulatory measures (Mikszta et al., 2006).

Injection Molding

Injection molding is a highly versatile technique for manufacturing microneedles. When combined with hot embossing, it enables the production of hollow polycarbonate-based microneedles that offer exceptional puncture resistance while maintaining sharpness, even after multiple insertions and withdrawals (Arbós et al., 2002). Micro-injection molding can also be utilized to produce solid microneedles that can effectively transport high-molecular-weight molecules (Donnelly et al., 2014). Polymer-based microneedles fabricated through this method have proven capable of penetrating human skin tissue and effectively extracting fluids. Moreover, this technique offers a cost-efficient solution for the large-scale production of microneedles (Larrañeta et al., 2016).

Laser Cutting

The fabrication of metal microneedles is typically achieved through advanced techniques such as 3D laser cutting, laser ablation, and electroplating. The process often begins with infrared-laser-cut stainless steel or titanium sheets, utilizing designs generated from Computer-Aided Design (CAD) software to ensure precision and consistency in manufacturing (Hong et al., 2013). These post-processed mass-produced microneedle arrays are cleaned, bent, and polished to make their shape finer so that they can function in the best possible way. This provides the possibility of single-row or multi-row arrays of microneedles of practically any geometry (Chu et al., 2010).

Atomized Spraying Method

This atomized spray technique holds the potential to revolutionize the production of dissolvable microneedles with customizable shapes and properties. Freed from the limitations of surface tension and viscosity, this method enables the fabrication of microneedles from a wide range of materials, including sugars and polymers (Donnelly et al., 2010). The atomized spray is sprayed into PDMS molds and dries to form the desired microneedle structure. This process enables the fabrication of a layer-by-layer microneedle with various properties, and thus has more control over active substance release (Gaikwad and Desai, 2018).

Drug delivery by microneedles

Vaccines formation

Traditional vaccines are primarily administered through subcutaneous injection. However, recent research highlights microneedles as a promising vaccine delivery platform, as they can directly present antigens to dendritic cells in the skin, eliciting a stronger immune response. Unlike traditional vaccines, microneedle-based vaccines also offer the advantage of being less reliant on refrigeration for storage (Gaikwad et al., 2020). Monoclonal antibodies are powerful agents with significant diagnostic and therapeutic applications, including delivery through microneedles. They enable precise targeting of specific cells for immune system modulation, minimizing the over-activation of autoreactive T cells and reducing adverse side effects. However, challenges such as protein inactivation and diminished efficacy remain key concerns in their application in Table 1 (Odujole and Desai, 2020).

Table 1: Comparison of microneedles over parenteral dosages forms.
Sl. No.ParameterMicroneedleParenteralReferences
1Invasiveness and PainThese microneedles are actually very fine and should penetrate only up to the top layers of the skin, excluding deeper tissues and blood vessels. It thus causes little to almost negligible pain and can significantly reduce the fear and discomfort a patient endures, especially for needle-phobic patients.These methods, namely the subcutaneous, intramuscular and intravenous injections, require deeper penetration into muscle, fat, or veins and, hence, generally painful or uncomfortable. Intramuscular injections may even result in tenderness, while intravenous injections might cause distress from the access in a vein.(Prausnitz, 2004).
2Drug Delivery Efficiency and BioavailabilityMicroneedles bypass the stratum corneum, directly depositing drugs into the epidermis or dermis where it could be absorbed into systemic circulation. Thus, higher bioavailability as compared with most oral routes can be expected, though delivery will not be faster than intravenous administration. Penetration depth and drug release are controllable, and microneedles can deliver a wide variety of molecules, including vaccines, peptides, and small molecules.Parenteral injections are for the most part intravenous, hence they give a 100% bioavailability. Though Subcutaneous and Intramuscular injections also give high bioavailability, the rate of absorption is slower as compared to IVs. With parenteral methods, a broad range of drugs could be administered, such as biologics, chemotherapeutics, and vaccines, therefore parenteral are useful to provide systemic and rapid drug effects.(Prasad and Koul, 2012).
3Safety and Risk of ComplicationsMicroneedles are less likely to cause infection as compared to parenteral injections because they do not prick deeper into the skin or blood. Moreover, the shallow non-penetrating nature of the instrument also helps it avoid blood vessels, which further reduces the risk of contamination and infection. Dissolvable microneedles also avoid sharp objects risk factors; hence, they reduce the risks of needle-stick injuries and consequently the biohazard waste.The risk of infection, phlebitis, or extravasation is greater with parenteral methods, particularly intravenous injections. Localized reactions to subcutaneous and intramuscular injections can include pain, bruising, or abscess formation. Perhaps one of the most serious risks to health care workers is needle-stick injury.(Mistilis et al., 2015).
Speed of Drug ActionThe slow and controlled release of drugs through microneedles is quite effective for vaccines and long-term therapies. However, their activity onset usually is not as quick as intravenous administration because their effect is based on the absorption through the various layers of the skin and local circulation.The drug is administered directly into the bloodstream, thus intravenous injection provides the fastest onset of drug action. This is very important for emergencies or when immediate systemic effects are needed (for example, anesthesia, antibiotics in critical care). In comparison, intramuscular and subcutaneous injections offer slower absorption but still faster than transdermal routes.(Jung and Jin, 2021).
Drug Stability and Cold Chain RequirementsDissolvable polymers-based microneedle patches offer the advantage of improved drug stability, thereby eliminating or minimizing refrigeration requirements-the major logistics headache of vaccine transportation. This is a critical requirement for vaccines. It makes them ideal for use in resource-poor settings or mass immunization campaigns.Most biologics, vaccines, and insulin rely on strict cold chain management to ensure stability. This involves high logistical complexity and cost, particularly in remote or underdeveloped areas. Some parenteral formulations are not very stable in non-sterile conditions.(Heneweer et al., 2012).
Application and CostMicroneedles are mass-producible at relatively low expense, especially dissolvable microneedles made from inexpensive polymers. The scalability and ease of use for mass drug delivery-even in low-resource public health settings-are the cost-effectiveness reasons associated with the cost to deliver drugs at scale. At the same time, microneedle use is associated with reduced healthcare costs related to the clinical administration process.Parenteral injections generally require more resources, such as sterilized equipment, healthcare professionals and more complex manufacturing processes. It is also much more costly, especially with intravenous therapy and the possibility of hospitalization or medical observation.(Li et al., 2018).

This study reveals that the merging of trehalose and the parent formulation in microneedles significantly improves stability in comparison to that produced with sucrose (Odujole and Desai, 2020). Trehalose treatment helps preserve antibody integrity even under harsh conditions, such as prolonged exposure to high temperatures. Additionally, delivering GM-CSF through microneedles can significantly enhance immunogenicity and extend the duration of the antibody response (Saurer et al., 2010). Microneedles made of various materials consisting of trehalose, Carboxymethyl Cellulose (CMC), and gelatin have been proven to be suitable for stable GM-CSF delivery (Griss et al., 2001). The third-generation hepatitis vaccine was also demonstrated to be administered through microneedles consisting of 15% trehalose. In comparison to a liquid vaccine, it was found in this study that it remained viable at higher temperatures and multiple freeze-thaw cycles (Gaikwad and Desai, 2021).

This highlights the potential of vaccines and antibody delivery via microneedles to achieve optimal healthcare outcomes through superior efficacy, convenience, and stability in drug administration (Madou, 2018).

Proteins Regulation

Protein drugs serve as essential therapeutic agents for treating various cancers, genetic disorders, and related diseases. However, challenges such as stability, absorption, and large molecular size have hindered their overall therapeutic effectiveness (Plummer, 2009). The microneedles hold great promise for protein delivery and overcome some of the limitations associated with traditional delivery systems. The microneedles have the ability to avoid the digestive tract by delivering the protein drugs into the body via the skin directly, thus enhancing absorption and reducing degradation (Tran and Nguyen, 2017). This method has been successfully utilized to deliver a diverse range of protein pharmaceuticals, including insulin, desmopressin, erythropoietin, lysozyme, glucagon, glucagon-like peptide-1, parathyroid hormone, and growth hormone, with remarkable effectiveness. Ensuring protein stability throughout production, storage, and delivery is crucial for maintaining therapeutic efficacy (Lycke, 2012). Temperature, humidity, and the inclusion of stabilizers can significantly impact protein integrity. However, recent advancements in microneedle stability have been remarkable. For example, glucose-sensitive microneedles loaded with phenylboronic acid, which exhibit enhanced thermal stability, have successfully delivered insulin to diabetic patients with precision and effectiveness (Adarkwa and Desai, 2016).

Careful optimization of microneedle manufacturing parameters is essential to preserve protein activity and efficacy. Research has shown that factors such as temperature control, drying conditions, polymer concentration, and the incorporation of protein stabilizers play a crucial role in enhancing protein stability (Desai et al., 2012). Under optimized conditions, lysozyme activity was remarkably retained at 99.8±3.8%. These findings highlight the groundbreaking potential of microneedles in the efficient delivery of protein-based drug (Huang and Fu, 2007). New discoveries in this field address challenges associated with conventional delivery methods, paving the way for enhanced therapeutic outcomes and improved patient care. These advancements hold immense potential for revolutionizing drug delivery and treatment efficacy (Suzuki et al., 2018).

Applications of Microneedles

Vaccine Delivery

Dissolvable microneedles represent a groundbreaking vaccine delivery platform, offering a superior alternative to conventional hypodermic needles. They are biocompatible, durable, and highly scalable, with key advantages such as the elimination of biohazardous waste. To date, dissolvable microneedles have been successfully employed for vaccine delivery against numerous diseases, including malaria, diphtheria, influenza, hepatitis B, HIV, and polio (McKenzie and Desai, 2018). While dissolvable microneedles have gained significant popularity, coated microneedles have also demonstrated remarkable potential. Studies have reported enhanced immunogenicity in pigs following immunization with the BCG vaccine using coated microneedles (Prausnitz, 2017). DNA vaccines coated onto microneedles and administered intradermally have been shown to effectively prime cytotoxic lymphocytes in mice. Additionally, coated microneedles have been successfully utilized for influenza vaccination, further demonstrating their potential in immunization strategies in Table 2 (Desai et al., 2015).

Table 2: Comparison of microneedles over transdermal patch.
Sl. No.ParameterMicroneedleTransdermal PatchReferences
1Drug delivery mechanismThese are tiny, needle-like projections known as microneedles that penetrate either the epidermis or dermis to inject drugs directly into the outermost layer of the skin. These produce minute channels bypassing the skin barrier and thus allow the delivery of a much greater range of drugs, thereby including large molecules such as proteins, peptides, and vaccines.Small, lipophilic molecules utilize passive diffusion through the skin in delivering activity from transdermal patches. However, there is an important barrier in the stratum corneum that restricts the size and the type of drugs delivered via patches. Hydrophilic or larger molecules cannot permeate the skin by traditional patch delivery systems.(Prasad and Koul, 2012).
2Range of Drugs DeliveredThese can release a wide variety of drugs ranging from small molecules to large proteins, DNA, vaccines, and peptides. Since they may deliver drugs deeper into the skin, they are of special interest for applying biologics, hydrophilic drugs, and even gene therapies.Only small, lipophilic drugs can cross the skin from patches. Since these can diffuse past the permeability barrier, a strong limitation exists in this respect on the drug variety that can be delivered via patches.(Vandervoort and Ludwig, 2008).
3Drug absorption and efficiencyThey are valid for vaccines, insulin, and other biologics that require accurate dosing since they bypass the skin's natural barrier to deliver drugs straight into the dermis or epidermis, leading to fast and efficient drug absorption.With passive diffusion through the skin, the absorption of drug from patches is slow and variable. It is usually lower than that in other routs of administration, and efficiency will depend upon the drug's permeability in the skin.(Prausnitz, 2004).
4Dosing Precision and ControlSuch microneedles can offer precise dosing control by governing the depth of penetration and size of needle array. In particular, some microneedles are designed to degrade in the skin, thereby enabling controlled drug delivery over time.Patches can deliver drugs continuously over an extended period and are appropriate for drugs that must be maintained in plasma at a steady level (e.g., nicotine, hormones). Poorer control of drug delivery sometimes results because skin permeability varies between patients.(Sullivan et al., 2010)
5Application and Self-AdministrationThey are often designed to be self-administered, particularly true for the case of microneedle patches. That makes them outstanding for vaccines and chronic conditions in which frequent dosing is required. In some formulations, such as dissolvable microneedles, sharps disposal is not required.Patches are designed for simple self-application, allowing patients to use them with minimal training. They are widely used in long-term drug therapies, such as hormone replacement and nicotine cessation.(Jung and Jin, 2021).
6Patient experienceThe use of microneedles provides a painless minimally invasive approach without causing any pain. Insertion of these microneedles is painless because, unlike the normal hypodermic needle, they do not pierce the pain receptors located deeper within the skin layers. Patient tolerance is therefore ideal, which leads to more compliance.Patches are non-invasive and painless, but the range of drugs they can deliver is limited. Their passive nature makes them highly acceptable to patients, though some users may experience irritation or allergic reactions to the adhesives.(Yanes and Tamanoi, 2012).

Hollow microneedles are another promising vaccine delivery platform, successfully used in animal studies to administer anthrax and plague vaccines, effectively inducing protective immunity (Desai et al., 2013). In a clinical human setting, a microneedle for the purpose of influenza vaccination elicited immune responses that were similar to those elicited by intramuscular injection; in this sense, microneedles hold promise as a substitute for the conventional mode of needle-delivery of vaccines (Ahmed et al., 2020). Their biocompatibility, durability, and scalability make them highly suitable for a wide range of vaccines. Ongoing research and development in this field will continue to unveil innovative applications of microneedles, advancing vaccine delivery and strengthening public health efforts (Ismail et al., 2020).

Drug Delivery

Since their introduction in 1998, microneedles have rapidly evolved into a groundbreaking platform for transdermal drug delivery. Over time, various types of microneedles have emerged, including dissolvable, coated, and solid microneedles, each capable of delivering drugs for a wide range of medical applications. Dissolvable microneedle patches have been successfully used for the delivery of human growth hormone and caffeine, offering potential treatments for conditions such as obesity and growth disorders. Coated microneedles have facilitated the delivery of salmon calcitonin, while solid microneedles have been employed for the administration of protein antigens, with ovalbumin serving as a notable example (Menazea et al., 2021; Mostafa et al., 2020). Solid silicon and metal microneedles have demonstrated exceptional efficacy in delivering various compounds through the skin, including calcein, BSA, and insulin. Microneedles have significantly enhanced the transdermal permeation of numerous medications, such as ibuprofen, ketoprofen, and paracetamol. Additionally, they have been successfully utilized for the delivery of ascorbic acid, riboflavin, aspirin, docetaxel, pilocarpine, lidocaine hydrochloride, and glycerol, further showcasing their versatility in drug administration (Nejad et al., 2020; Aoyagi et al., 2007). While significant focus has been placed on skin penetration in both animals and humans, microneedles have also demonstrated their capability for drug delivery into deeper tissues, including chicken thighs and brain tissue. This underscores their versatility and immense potential for diverse drug delivery applications (Prausnitz and Langer, 2008).

Cosmetic Application

Microneedles have emerged as an important delivery platform in cosmetic medicine. One of the applications where new innovation has been created is the delivery of hyaluronic acid, which actually is an essential component of skin hydration, for improved health and appearance of skin (Kim et al., 2018). Dissolvable microneedle patches have been developed which deliver hyaluronic acid, other beneficial compounds, like ascorbic acid, and retinyl retinoate directly into the skin. Treatment with facial hair growth has also shown promise in some studies (Park et al., 2005). A study aimed at demonstrating the enhancement of delivery of eflornithine, a drug used in treating facial hirsutism, has proven the effectiveness of solid microneedles in in vitro as well as in vivo analysis. Apart from skin rejuvenation and hair growth, microneedles have been studied for their treatment of alopecia areata, an autoimmune condition causing hair loss (Lhernould et al., 2015). In clinic studies, there have been benefits observed; hair growth has been seen in patients who received this form of treatment. Another application of microneedles has been in the treatment of skin conditions other than keloid scars, such as atrophic facial scarring, atrophic acne scars, and hypertrophic burn scars (Sammoura et al., 2007). Since direct access to target sites is made possible through penetration and delivery of active ingredients in the skin via microneedles, they are useful for treatment applications for such cosmetic conditions as well (Gill and Prausnitz, 2007).

CONCLUSION

One of the most promising transdermal drug delivery systems that have recently gained much popularity with regards to its ability to improve access to medications for patients through providing an alternative for more traditional methods of administration is the MNs. There are several types of MNs, including those that are solid and coated, dissolvable, and hydro gel-based formulations; they can also be produced from silicon, metals, polymers, glass, and ceramics. A broad variety of manufacturing methods has been employed to fabricate the microneedles in wide ranges of geometrical dimensions and specifically tailored properties to meet the varied requirements for medical purposes. As the technology develops, it has become the mainstay of many clinical trials and studies for drug delivery purposes. Most of the research outcomes have been reported to be successful, especially in regard to promising a great potential of delivering therapeutic agents across a range of applications.

REFERENCES

As published

Showing references and in-text citations exactly as published.

  1. 1.Adarkwa, E.; Desai, S.. Scalable droplet based manufacturing using in-flight laser evaporation. Journal of Nanoengineering and Nanomanufacturing. 2016;6(2):87–92. https://doi.org/10.1166/jnan.2016.1265DOIGOOGLE SCHOLAR
  2. 2.Ahmed, M. K.; El-Naggar, M. E.; Aldalbahi, A.; El-Newehy, M. H.; Menazea, A. A.. Methylene blue degradation under visible light of metallic nanoparticles scattered into graphene oxide using laser ablation technique in aqueous solutions. Journal of Molecular Liquids. 2020;315:Article 113794. https://doi.org/10.1016/j.molliq.2020.113794DOIGOOGLE SCHOLAR
  3. 3.Al Sulaiman, D.; Chang, J. Y. H.; Bennett, N. R.; Topouzi, H.; Higgins, C. A.; Irvine, D. J. et al. Hydrogel-coated microneedle arrays for minimally invasive sampling and sensing of specific circulating nucleic acids from skin interstitial fluid. ACS Nano. 2019;13(8):9620–9628. https://doi.org/10.1021/acsnano.9b04783DOIGOOGLE SCHOLAR
  4. 4.Aldawood, F. K.; Andar, A.; Desai, S.. A comprehensive review of microneedles: Types, materials, processes, characterizations and applications. Polymers. 2021;13(16):2815. https://doi.org/10.3390/polym13162815DOIGOOGLE SCHOLAR
  5. 5.Amorij, J.-P.; Hinrichs, W. Lj.; Frijlink, H. W.; Wilschut, J. C.; Huckriede, A.. Needle-free influenza vaccination. The Lancet. Infectious Diseases. 2010;10(10):699–711. https://doi.org/10.1016/S1473-3099(10DOIGOOGLE SCHOLAR
  6. 6.Aoyagi, S.; Izumi, H.; Isono, Y.; Fukuda, M.; Ogawa, H.. Laser fabrication of high aspect ratio thin holes on biodegradable polymer and its application to a microneedle. Sensors and Actuators A. 2007;139(1-2):293–302. https://doi.org/10.1016/j.sna.2006.11.022DOIGOOGLE SCHOLAR
  7. 7.Arbós, P.; Wirth, M.; Arangoa, M. A.; Gabor, F.; Irache, J. M.. Gantrez® AN as a new polymer for the preparation of ligand–nanoparticle conjugates. Journal of Controlled Release. 2002;83(3):321–330. https://doi.org/10.1016/s0168-3659(02DOIGOOGLE SCHOLAR
  8. 8.Badran, M. M.; Kuntsche, J.; Fahr, A.. Skin penetration enhancement by a microneedle device (Dermaroller®) in vitro: Dependency on needle size and applied formulation. European Journal of Pharmaceutical Sciences. 2009;36(4–5):511–523. https://doi.org/10.1016/j.ejps.2008.12.008DOIGOOGLE SCHOLAR
  9. 9.Banga, A. K.. Microporation applications for enhancing drug delivery. Expert Opinion on Drug Delivery. 2009;6(4):343–354. https://doi.org/10.1517/17425240902841935DOIGOOGLE SCHOLAR
  10. 10.Bediz, B.; Korkmaz, E.; Khilwani, R.; Donahue, C.; Erdos, G.; Falo, L. D. et al. Dissolvable microneedle arrays for intradermal delivery of biologics: Fabrication and application. Pharmaceutical Research. 2014;31(1):117–135. https://doi.org/10.1007/s11095-013-1137-xDOIGOOGLE SCHOLAR
  11. 11.Bhatnagar, S.; Dave, K.; Venuganti, V. V. K.. Microneedles in the clinic. Journal of Controlled Release. 2017;260:164–182. https://doi.org/10.1016/j.jconrel.2017.05.029DOIGOOGLE SCHOLAR
  12. 12.Boehm, R. D.; Miller, P. R.; Singh, R.; Shah, A.; Stafslien, S.; Daniels, J. et al. Indirect rapid prototyping of antibacterial acid anhydride copolymer microneedles. Biofabrication. 2012;4(1):Article 011002. https://doi.org/10.1088/1758-5082/4/1/011002DOIGOOGLE SCHOLAR
  13. 13.Bystrova, S.; Luttge, R.. Micromolding for ceramic microneedle arrays. Microelectronic Engineering. 2011;88(8):1681–1684. https://doi.org/10.1016/j.mee.2010.12.067DOIGOOGLE SCHOLAR
  14. 14.Choy, Y. B.; Prausnitz, M. R.. The rule of five for non-oral routes of drug delivery: Ophthalmic, inhalation and transdermal. Pharmaceutical Research. 2011;28(5):943–948. https://doi.org/10.1007/s11095-010-0292-6DOIGOOGLE SCHOLAR
  15. 15.Chu, L. Y.; Choi, S.-O.; Prausnitz, M. R.. Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs. Journal of Pharmaceutical Sciences. 2010;99(10):4228–4238. https://doi.org/10.1002/jps.22140DOIGOOGLE SCHOLAR
  16. 16.Cormier, M.; Johnson, B.; Ameri, M.; Nyam, K.; Libiran, L.; Zhang, D. D. et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. Journal of Controlled Release. 2004;97(3):503–511. https://doi.org/10.1016/j.jconrel.2004.04.003DOIGOOGLE SCHOLAR
  17. 17.Coulman, S.; Allender, C.; Birchall, J.. Microneedles and other physical methods for overcoming the stratum corneum barrier for cutaneous gene therapy. Critical Reviews in Therapeutic Drug Carrier Systems. 2006;23(3):205–258. https://doi.org/10.1615/critrevtherdrugcarriersyst.v23.i3.20DOIGOOGLE SCHOLAR
  18. 18.Daddona, P. E.; Matriano, J. A.; Mandema, J.; Maa, Y.-F.. Parathyroid hormone (1–34)-coated microneedle patch system: Clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis. Pharmaceutical Research. 2011;28(1):159–165. https://doi.org/10.1007/s11095-010-0192-9DOIGOOGLE SCHOLAR
  19. 19.De Desai, S. P.; Gomes, F.. Design for nano/micro manufacturing: A holistic approach towards achieving manufacturing excellence. Journal of Udyog Pragati. 2015;39(2):18–25.GOOGLE SCHOLAR
  20. 20.Desai, S.; Bidanda, B.; Bártolo, P. J.. Emerging trends in the applications of metallic and ceramic biomaterials. Bio-materials and prototyping applications in medicine. Springer International Publishing. 2021;1–17. https://doi.org/10.1007/978-3-030-35876-1_1DOIGOOGLE SCHOLAR
  21. 21.Desai, S.; Craps, M.; Esho, T.. Direct writing of nanomaterials for flexible thin-film transistors (fTFTs). The International Journal of Advanced Manufacturing Technology. 2013;64(1–4):537–543. https://doi.org/10.1007/s00170-012-4425-4DOIGOOGLE SCHOLAR
  22. 22.Desai, S.; Esho, T.; Kaware, R.. Experimental investigation of controlled microdroplet evaporation toward scalable micro/nanomanufacturing. IIE Transactions. 2012;44(2):155–162. https://doi.org/10.1080/0740817X.2011.593610DOIGOOGLE SCHOLAR
  23. 23.Dharadhar, S.; Majumdar, A.; Dhoble, S.; Patravale, V.. Microneedles for transdermal drug delivery: A systematic review. Drug Development and Industrial Pharmacy. 2019;45(2):188–201. https://doi.org/10.1080/03639045.2018.1539497DOIGOOGLE SCHOLAR
  24. 24.Donnelly, R.; Douroumis, D.. Microneedles for drug and vaccine delivery and patient monitoring. Drug Delivery and Translational Research. 2015;5(4):311–312. https://doi.org/10.1007/s13346-015-0250-2DOIGOOGLE SCHOLAR
  25. 25.Donnelly, R. F.; Morrow, D. I. J.; McCrudden, M. T. C.; Alkilani, A. Z.; Vicente-Pérez, E. M.; O’Mahony, C. et al. Hydrogel-forming and dissolving microneedles for enhanced delivery of photosensitizers and precursors. Photochemistry and Photobiology. 2014;90(3):641–647. https://doi.org/10.1111/php.12209DOIGOOGLE SCHOLAR
  26. 26.Donnelly, R. F.; Raj Singh, T. R. R.; Woolfson, A. D.. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety. Drug Delivery. 2010;17(4):187–207. https://doi.org/10.3109/10717541003667798DOIGOOGLE SCHOLAR
  27. 27.Edens, C.; Collins, M. L.; Goodson, J. L.; Rota, P. A.; Prausnitz, M. R.. A microneedle patch containing measles vaccine is immunogenic in non-human primates. Vaccine. 2015;33(37):4712–4718. https://doi.org/10.1016/j.vaccine.2015.02.074DOIGOOGLE SCHOLAR
  28. 28.Engelke, L.; Winter, G.; Hook, S.; Engert, J.. Recent insights into cutaneous immunization: How to vaccinate via the skin. Vaccine. 2015;33(37):4663–4674. https://doi.org/10.1016/j.vaccine.2015.05.012DOIGOOGLE SCHOLAR
  29. 29.Gaikwad, A.; Desai, S.. Understanding material deformation in nanoimprint of gold using Molecular Dynamics simulations. American Journal of Engineering and Applied Sciences. 2018;11(2):837–844. https://doi.org/10.3844/ajeassp.2018.837.844DOIGOOGLE SCHOLAR
  30. 30.Gaikwad, A.; Desai, S.. Molecular dynamics investigation of the deformation mechanism of gold with variations in mold profiles during nanoimprinting. Materials. 2021;14(10):2548. https://doi.org/10.3390/ma14102548DOIGOOGLE SCHOLAR
  31. 31.Gaikwad, A.; Odujole, J.; Desai, S.. Atomistic investigation of process parameter variations on material deformation behavior in nanoimprint lithography of gold. Precision Engineering. 2020;64:7–19. https://doi.org/10.1016/j.precisioneng.2020.03.007DOIGOOGLE SCHOLAR
  32. 32.Gill, H. S.; Prausnitz, M. R.. Coated microneedles for transdermal delivery. Journal of Controlled Release. 2007;117(2):227–237. https://doi.org/10.1016/j.jconrel.2006.10.017DOIGOOGLE SCHOLAR
  33. 33.Griss, P.; Enoksson, P.; Tolvanen-Laakso, H. K.; Merilainen, P.; Ollmar, S.; Stemme, G.. Micromachined electrodes for biopotential measurements. Journal of Microelectromechanical Systems. 2001;10(1):10–16. https://doi.org/10.1109/84.911086DOIGOOGLE SCHOLAR
  34. 34.Haj-Ahmad, R.; Khan, H.; Arshad, M. S.; Rasekh, M.; Hussain, A.; Walsh, S. et al. Microneedle coating techniques for transdermal drug delivery. Pharmaceutics. 2015;7(4):486–502. https://doi.org/10.3390/pharmaceutics7040486DOIGOOGLE SCHOLAR
  35. 35.Harvey, A. J.; Kaestner, S. A.; Sutter, D. E.; Harvey, N. G.; Mikszta, J. A.; Pettis, R. J.. Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. Pharmaceutical Research. 2011;28(1):107–116. https://doi.org/10.1007/s11095-010-0123-9DOIGOOGLE SCHOLAR
  36. 36.He, R.; Niu, Y.; Li, Z.; Li, A.; Yang, H.; Xu, F. et al. A hydrogel microneedle patch for point-of-care testing based on skin interstitial fluid. Advanced Healthcare Materials. 2020;9(4):Article e1901201. https://doi.org/10.1002/adhm.201901201DOIGOOGLE SCHOLAR
  37. 37.Heneweer, C.; Gendy, S. E. M.; Peñate-Medina, O.. Liposomes and inorganic nanoparticles for drug delivery and cancer imaging. Therapeutic Delivery. 2012;3(5):645–656. https://doi.org/10.4155/tde.12.38DOIGOOGLE SCHOLAR
  38. 38.Hirobe, S.; Azukizawa, H.; Hanafusa, T.; Matsuo, K.; Quan, Y.-S.; Kamiyama, F. et al. Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. Biomaterials. 2015;57:50–58. https://doi.org/10.1016/j.biomaterials.2015.04.007DOIGOOGLE SCHOLAR
  39. 39.Hong, X.; Wei, L.; Wu, F.; Wu, Z.; Chen, L.; Liu, Z. et al. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Design, Development and Therapy. 2013;7:945–952. https://doi.org/10.2147/DDDT.S44401DOIGOOGLE SCHOLAR
  40. 40.Huang, H.; Fu, C.. Different fabrication methods of out-of-plane polymer hollow needle arrays and their variations. Journal of Micromechanics and Microengineering. 2007;17(2):393–402. https://doi.org/10.1088/0960-1317/17/2/027DOIGOOGLE SCHOLAR
  41. 41.Indermun, S.; Luttge, R.; Choonara, Y. E.; Kumar, P.; Du Toit, L. C.; Modi, G. et al. Current advances in the fabrication of microneedles for transdermal delivery. Journal of Controlled Release. 2014;185:130–138. https://doi.org/10.1016/j.jconrel.2014.04.052DOIGOOGLE SCHOLAR
  42. 42.Ismail, A. M.; El-Newehy, M. H.; El-Naggar, M. E.; Meera Moydeen, A. M.; Menazea, A. A.. Enhancement the electrical conductivity of the synthesized polyvinylidene fluoride/polyvinyl chloride composite doped with palladium nanoparticles via laser ablation. Journal of Materials Research and Technology. 2020;9(5):11178–11188. https://doi.org/10.1016/j.jmrt.2020.08.013DOIGOOGLE SCHOLAR
  43. 43.Ita, K.. Transdermal delivery of drugs with microneedles-Potential and challenges. Pharmaceutics. 2015;7(3):90–105. https://doi.org/10.3390/pharmaceutics7030090DOIGOOGLE SCHOLAR
  44. 44.Jeong, H.-R.; Lee, H.-S.; Choi, I.-J.; Park, J.-H.. Considerations in the use of microneedles: Pain, convenience, anxiety and safety. Journal of Drug Targeting. 2017;25(1):29–40. https://doi.org/10.1080/1061186X.2016.1200589DOIGOOGLE SCHOLAR
  45. 45.Jiang, J.; Gill, H. S.; Ghate, D.; McCarey, B. E.; Patel, S. R.; Edelhauser, H. F. et al. Coated microneedles for drug delivery to the eye. Investigative Ophthalmology and Visual Science. 2007;48(9):4038–4043. https://doi.org/10.1167/iovs.07-0066DOIGOOGLE SCHOLAR
  46. 46.Jiang, J.; Moore, J. S.; Edelhauser, H. F.; Prausnitz, M. R.. Intrascleral drug delivery to the eye using hollow microneedles. Pharmaceutical Research. 2009;26(2):395–403. https://doi.org/10.1007/s11095-008-9756-3DOIGOOGLE SCHOLAR
  47. 47.Jung, J. H.; Jin, S. G.. Microneedle for transdermal drug delivery: Current trends and fabrication. Journal of Pharmaceutical Investigation. 2021;51(5):503–517. https://doi.org/10.1007/s40005-021-00512-4DOIGOOGLE SCHOLAR
  48. 48.Kendall, M. A. F.; Chong, Y.-F.; Cock, A.. The mechanical properties of the skin epidermis in relation to targeted gene and drug delivery. Biomaterials. 2007;28(33):4968–4977. https://doi.org/10.1016/j.biomaterials.2007.08.006DOIGOOGLE SCHOLAR
  49. 49.Kim, M. J.; Park, S. C.; Rizal, B.; Guanes, G.; Baek, S.-K.; Park, J.-H. et al. Fabrication of circular obelisk-type multilayer microneedles using micro-milling and spray deposition. Frontiers in Bioengineering and Biotechnology. 2018;6:54. https://doi.org/10.3389/fbioe.2018.00054DOIGOOGLE SCHOLAR
  50. 50.Kim, Y.-C.; Park, J.-H.; Prausnitz, M. R.. Microneedles for drug and vaccine delivery. Advanced Drug Delivery Reviews. 2012;64(14):1547–1568. https://doi.org/10.1016/j.addr.2012.04.005DOIGOOGLE SCHOLAR
  51. 51.Kochhar, J. S.; Tan, J. J. Y.; Kwang, Y. C.; Kang, L.; Kochhar, J. S.; Tan, J. J. et al. Recent trends in microneedle development and applications in medicine and cosmetics (2013–2018). In Microneedles for transdermal drug delivery. Springer International Publishing. 2019;95–144. https://doi.org/10.1007/978-3-030-15444-8_7DOIGOOGLE SCHOLAR
  52. 52.Larrañeta, E.; Lutton, R. E. M.; Woolfson, A. D.; Donnelly, R. F.. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Materials Science and Engineering: R: Reports. 2016;104:1–32. https://doi.org/10.1016/j.mser.2016.03.001DOIGOOGLE SCHOLAR
  53. 53.Lee, K.; Lee, H. C.; Lee, D.-S.; Jung, H.. Drawing lithography: Three-dimensional fabrication of an ultrahigh-aspect-ratio microneedle. Advanced Materials. 2010;22(4):483–486. https://doi.org/10.1002/adma.200902418DOIGOOGLE SCHOLAR
  54. 54.Lhernould, M. S.; Deleers, M.; Delchambre, A.. Hollow polymer microneedles array resistance and insertion tests. International Journal of Pharmaceutics. 2015;480(1–2):152–157. https://doi.org/10.1016/j.ijpharm.2015.01.019DOIGOOGLE SCHOLAR
  55. 55.Li, S.; Li, W.; Prausnitz, M.. Individually coated microneedles for co-delivery of multiple compounds with different properties. Drug Delivery and Translational Research. 2018;8(5):1043–1052. https://doi.org/10.1007/s13346-018-0549-xDOIGOOGLE SCHOLAR
  56. 56.Lycke, N.. Recent progress in mucosal vaccine development: Potential and limitations. Nature Reviews. Immunology. 2012;12(8):592–605. https://doi.org/10.1038/nri3251DOIGOOGLE SCHOLAR
  57. 57.Ma, G.; Wu, C.. Microneedle, bio-microneedle and bio-inspired microneedle: A review. Journal of Controlled Release. 2017;251:11–23. https://doi.org/10.1016/j.jconrel.2017.02.011DOIGOOGLE SCHOLAR
  58. 58.Ma, Y.; Tao, W.; Krebs, S. J.; Sutton, W. F.; Haigwood, N. L.; Gill, H. S.. Vaccine delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity. Pharmaceutical Research. 2014;31(9):2393–2403. https://doi.org/10.1007/s11095-014-1335-1DOIGOOGLE SCHOLAR
  59. 59.Madou, M. J.. Fundamentals of microfabrication p. CRC Press. 2018;752. https://doi.org/10.1201/9781482274004DOIGOOGLE SCHOLAR
  60. 60.Marquetti, I.; Desai, S.. Orientation effects on the nanoscale adsorption behavior of bone morphogenetic protein-2 on hydrophilic silicon dioxide. RSC Advances. 2019;9(2):906–916. https://doi.org/10.1039/c8ra09165jDOIGOOGLE SCHOLAR
  61. 61.Martanto, W.; Davis, S. P.; Holiday, N. R.; Wang, J.; Gill, H. S.; Prausnitz, M. R.. Transdermal delivery of insulin using microneedles in vivo. Pharmaceutical Research. 2004;21(6):947–952. https://doi.org/10.1023/b:pham.0000029282.44140.2eDOIGOOGLE SCHOLAR
  62. 62.Martanto, W.; Moore, J. S.; Kashlan, O.; Kamath, R.; Wang, P. M.; O’Neal, J. M. et al. Microinfusion using hollow microneedles. Pharmaceutical Research. 2006;23(1):104–113. https://doi.org/10.1007/s11095-005-8498-8DOIGOOGLE SCHOLAR
  63. 63.McAllister, D. V.; Allen, M. G.; Prausnitz, M. R.. Microfabricated microneedles for gene and drug delivery. Annual Review of Biomedical Engineering. 2000;2(1):289–313. https://doi.org/10.1146/annurev.bioeng.2.1.289DOIGOOGLE SCHOLAR
  64. 64.McAllister, D. V.; Wang, P. M.; Davis, S. P.; Park, J.-H.; Canatella, P. J.; Allen, M. G. et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(24):13755–13760. https://doi.org/10.1073/pnas.2331316100DOIGOOGLE SCHOLAR
  65. 65.McConville, A.; Hegarty, C.; Davis, J.. Mini-review: Assessing the potential impact of microneedle technologies on home healthcare applications. Medicines. 2018;5(2):50. https://doi.org/10.3390/medicines5020050DOIGOOGLE SCHOLAR
  66. 66.McKenzie, J.; Desai, S.. Investigating sintering mechanisms for additive manufacturing of conductive traces. American Journal of Engineering and Applied Sciences. 2018;11(2):652–662. https://doi.org/10.3844/ajeassp.2018.652.662DOIGOOGLE SCHOLAR
  67. 67.Menazea, A. A.; El-Newehy, M. H.; Thamer, B. M.; El-Naggar, M. E.. Preparation of antibacterial film-based biopolymer embedded with vanadium oxide nanoparticles using one-pot laser ablation. Journal of Molecular Structure. 2021;1225. https://doi.org/10.1016/j.molstruc.2020.129163DOIGOOGLE SCHOLAR
  68. 68.Mikszta, J. A.; Dekker, J. P.; Harvey, N. G.; Dean, C. H.; Brittingham, J. M.; Huang, J. et al. Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine. Infection and Immunity. 2006;74(12):6806–6810. https://doi.org/10.1128/IAI.01210-06DOIGOOGLE SCHOLAR
  69. 69.Mistilis, M. J.; Bommarius, A. S.; Prausnitz, M. R.. Development of a thermostable microneedle patch for influenza vaccination. Journal of Pharmaceutical Sciences. 2015;104(2):740–749. https://doi.org/10.1002/jps.24283DOIGOOGLE SCHOLAR
  70. 70.Monteiro-Riviere, N. A.. Structure and function of skin. In Toxicology of the skin. CRC Press. 2010;15–32. https://doi.org/10.3109/9781420079180-3DOIGOOGLE SCHOLAR
  71. 71.Mostafa, A. M.; Lotfy, V. F.; Mwafy, E. A.; Basta, A. H.. Influence of coating by Cu and Ag nanoparticles via pulsed laser deposition technique on optical, electrical and mechanical properties of cellulose paper. Journal of Molecular Structure. 2020;1203. https://doi.org/10.1016/j.molstruc.2019.127472DOIGOOGLE SCHOLAR
  72. 72.Nejad, H. R.; Sadeqi, A.; Kiaee, G.; Sonkusale, S.. Low cost and cleanroom-free fabrication of microneedles. Microsystems and Nanoengineering. 2018;4(1):1–7. https://doi.org/10.1038/micronano.2017.73DOIGOOGLE SCHOLAR
  73. 73.Niinomi, M.; Nakai, M.. Titanium-based biomaterials for preventing stress shielding between implant devices and bone. International Journal of Biomaterials. 2011;2011(1):Article 836587. https://doi.org/10.1155/2011/836587DOIGOOGLE SCHOLAR
  74. 74.Odujole, J.; Desai, S.. Atomistic investigation of material deformation behavior of polystyrene in nanoimprint lithography. Surfaces. 2020b;3(4):649–663. https://doi.org/10.3390/surfaces3040043DOIGOOGLE SCHOLAR
  75. 75.Odujole, J. I.; Desai, S.. Molecular dynamics investigation of material deformation behavior of PMMA in nanoimprint lithography. AIP Advances. 2020a;10(9):5102. https://doi.org/10.1063/5.0014458DOIGOOGLE SCHOLAR
  76. 76.Oh, J.-H.; Park, H.-H.; Do, K.-Y.; Han, M.; Hyun, D.-H.; Kim, C.-G. et al. Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein. European Journal of Pharmaceutics and Biopharmaceutics. 2008;69(3):1040–1045. https://doi.org/10.1016/j.ejpb.2008.02.009DOIGOOGLE SCHOLAR
  77. 77.O’Mahony, C.. Structural characterization and in vivo reliability evaluation of silicon microneedles. Biomedical Microdevices. 2014;16(3):333–343. https://doi.org/10.1007/s10544-014-9836-6DOIGOOGLE SCHOLAR
  78. 78.Park, J.-H.; Allen, M. G.; Prausnitz, M. R.. Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery. Journal of Controlled Release. 2005;104(1):51–66. https://doi.org/10.1016/j.jconrel.2005.02.002DOIGOOGLE SCHOLAR
  79. 79.Plummer, J. D.. Silicon VLSI technology: Fundamentals, practice and modeling. Pearson Education. 2009.GOOGLE SCHOLAR
  80. 80.Prasad, R.; Koul, V.. Transdermal delivery of methotrexate: Past, present and future prospects. Therapeutic Delivery. 2012;3(3):315–325. https://doi.org/10.4155/tde.12.3DOIGOOGLE SCHOLAR
  81. 81.Prausnitz, M. R.. Microneedles for transdermal drug delivery. Advanced Drug Delivery Reviews. 2004;56(5):581–587. https://doi.org/10.1016/j.addr.2003.10.023DOIGOOGLE SCHOLAR
  82. 82.Prausnitz, M. R.. Engineering microneedle patches for vaccination and drug delivery to skin. Annual Review of Chemical and Biomolecular Engineering. 2017;8(1):177–200. https://doi.org/10.1146/annurev-chembioeng-060816-101514DOIGOOGLE SCHOLAR
  83. 83.Prausnitz, M. R.; Langer, R.. Transdermal drug delivery. Nature Biotechnology. 2008;26(11):1261–1268. https://doi.org/10.1038/nbt.1504DOIGOOGLE SCHOLAR
  84. 84.Quinn, H. L.; Bonham, L.; Hughes, C. M.; Donnelly, R. F.. Design of a dissolving microneedle platform for transdermal delivery of a fixed-dose combination of cardiovascular drugs. Journal of Pharmaceutical Sciences. 2015;104(10):3490–3500. https://doi.org/10.1002/jps.24563DOIGOOGLE SCHOLAR
  85. 85.Raphael, A. P.; Crichton, M. L.; Falconer, R. J.; Meliga, S.; Chen, X.; Fernando, G. J. P. et al. Formulations for microprojection/microneedle vaccine delivery: Structure, strength and release profiles. Journal of Controlled Release. 2016;225:40–52. https://doi.org/10.1016/j.jconrel.2016.01.027DOIGOOGLE SCHOLAR
  86. 86.Rzhevskiy, A. S.; Singh, T. R. R.; Donnelly, R. F.; Anissimov, Y. G.. Microneedles as the technique of drug delivery enhancement in diverse organs and tissues. Journal of Controlled Release. 2018;270:184–202. https://doi.org/10.1016/j.jconrel.2017.11.048DOIGOOGLE SCHOLAR
  87. 87.Sammoura, F.; Kang, J.; Heo, Y.-M.; Jung, T.; Lin, L.. Polymeric microneedle fabrication using a microinjection molding technique. Microsystem Technologies. 2007;13(5–6):517–522. https://doi.org/10.1007/s00542-006-0204-1DOIGOOGLE SCHOLAR
  88. 88.Saurer, E. M.; Flessner, R. M.; Sullivan, S. P.; Prausnitz, M. R.; Lynn, D. M.. Layer-by-layer assembly of DNA- and protein-containing films on microneedles for drug delivery to the skin. Biomacromolecules. 2010;11(11):3136–3143. https://doi.org/10.1021/bm1009443DOIGOOGLE SCHOLAR
  89. 89.Shakya, A. K.; Ingrole, R. S. J.; Joshi, G.; Uddin, M. J.; Anvari, S.; Davis, C. M. et al. Microneedles coated with peanut allergen enable desensitization of peanut sensitized mice. Journal of Controlled Release. 2019;314:38–47. https://doi.org/10.1016/j.jconrel.2019.09.022DOIGOOGLE SCHOLAR
  90. 90.Sharma, D.. Microneedles: An approach in transdermal drug delivery: A review. Pharmatutor. 2018;6(1):7–15. https://doi.org/10.29161/PT.v6.i1.2018.7DOIGOOGLE SCHOLAR
  91. 91.Sullivan, S. P.; Koutsonanos, D. G.; del Pilar Martin, M.; Lee, J. W.; Zarnitsyn, V.; Choi, S.-O. et al. Dissolving polymer microneedle patches for influenza vaccination. Nature Medicine. 2010;16(8):915–920. https://doi.org/10.1038/nm.2182DOIGOOGLE SCHOLAR
  92. 92.Suzuki, M.; Takahashi, T.; Aoyagi, S.. 3D laser lithographic fabrication of hollow microneedle mimicking mosquitos and its characterisation. International Journal of Nanotechnology. 2018;15(1/2/3):157–173. https://doi.org/10.1504/IJNT.2018.089545DOIGOOGLE SCHOLAR
  93. 93.Thakur, R. R. S.; Tekko, I. A.; Al-Shammari, F.; Ali, A. A.; McCarthy, H.; Donnelly, R. F.. Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery. Drug Delivery and Translational Research. 2016;6(6):800–815. https://doi.org/10.1007/s13346-016-0332-9DOIGOOGLE SCHOLAR
  94. 94.Tibbitt, M. W.; Dahlman, J. E.; Langer, R.. Emerging frontiers in drug delivery. Journal of the American Chemical Society. 2016;138(3):704–717. https://doi.org/10.1021/jacs.5b09974DOIGOOGLE SCHOLAR
  95. 95.Tran, K. T. M.; Nguyen, T. D.. Lithography-based methods to manufacture biomaterials at small scales. Journal of Science: Advanced Materials and Devices. 2017;2(1):1–14. https://doi.org/10.1016/j.jsamd.2016.12.001DOIGOOGLE SCHOLAR
  96. 96.Traverso, G.; Schoellhammer, C. M.; Schroeder, A.; Maa, R.; Lauwers, G. Y.; Polat, B. E. et al. Microneedles for drug delivery via the gastrointestinal tract. Journal of Pharmaceutical Sciences. 2015;104(2):362–367. https://doi.org/10.1002/jps.24182DOIGOOGLE SCHOLAR
  97. 97.Vandervoort, J.; Ludwig, A.. Microneedles for transdermal drug delivery: A minireview. Frontiers in Bioscience: A Journal and Virtual Library. 2008;13(5):1711–1715. https://doi.org/10.2741/2794DOIGOOGLE SCHOLAR
  98. 98.Verbaan, F. J.; Bal, S. M.; Van den Berg, D. J.; Groenink, W. H. H.; Verpoorten, H.; Lüttge, R. et al. Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin. Journal of Controlled Release. 2007;117(2):238–245. https://doi.org/10.1016/j.jconrel.2006.11.009DOIGOOGLE SCHOLAR
  99. 99.Waghule, T.; Singhvi, G.; Dubey, S. K.; Pandey, M. M.; Gupta, G.; Singh, M. et al. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine and Pharmacotherapy. 2019;109:1249–1258. https://doi.org/10.1016/j.biopha.2018.10.078DOIGOOGLE SCHOLAR
  100. 100.Xiang, Z.; Yen, S.-C.; Xue, N.; Sun, T.; Tsang, W. M.; Zhang, S. et al. Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle. Journal of Micromechanics and Microengineering. 2014;24(6):Article 065015. https://doi.org/10.1088/0960-1317/24/6/065015DOIGOOGLE SCHOLAR
  101. 101.Yan, G.; Warner, K. S.; Zhang, J.; Sharma, S.; Gale, B. K.. Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery. International Journal of Pharmaceutics. 2010;391(1–2):7–12. https://doi.org/10.1016/j.ijpharm.2010.02.007DOIGOOGLE SCHOLAR
  102. 102.Yanes, R. E.; Tamanoi, F.. Development of mesoporous silica nanomaterials as a vehicle for anticancer drug delivery. Therapeutic Delivery. 2012;3(3):389–404. https://doi.org/10.4155/tde.12.9DOIGOOGLE SCHOLAR
  103. 103.Yang, S. Y.; O’Cearbhaill, E. D.; Sisk, G. C.; Park, K. M.; Cho, W. K.; Villiger, M. et al. A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue. Nature Communications. 2013;4(1):1702. https://doi.org/10.1038/ncomms2715DOIGOOGLE SCHOLAR
  104. 104.Ye, Y.; Yu, J.; Wen, D.; Kahkoska, A. R.; Gu, Z.. Polymeric microneedles for transdermal protein delivery. Advanced Drug Delivery Reviews. 2018;127:106–118. https://doi.org/10.1016/j.addr.2018.01.015DOIGOOGLE SCHOLAR
  105. 105.Yu, J.; Zhang, Y.; Ye, Y.; DiSanto, R.; Sun, W.; Ranson, D. et al. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(27):8260–8265. https://doi.org/10.1073/pnas.1505405112DOIGOOGLE SCHOLAR
  106. 106.Zhao, X.; Li, X.; Zhang, P.; Du, J.; Wang, Y.. Tip-loaded fast-dissolving microneedle patches for photodynamic therapy of subcutaneous tumor. Journal of Controlled Release. 2018;286:201–209. https://doi.org/10.1016/j.jconrel.2018.07.038DOIGOOGLE SCHOLAR

Cite this article

SELECT FORMAT

Ganguly, P., Saha, P., Khawas, S., Chatterjee, S., Patel, A. K., & Pati, P. P. (2026). An Overview on Microneedle Technology: Superior Pharmaceutical Transdermal Delivery Forms. International Journal of Pharmaceutical Investigation, 16(1), 77–88. https://doi.org/10.5530/ijpi.20260499