Biotin-Functionalized Lipid Nanoparticles: A Promising Approach for Gemcitabine Delivery in Non-Small Cell Lung Cancer Treatment

Abstract

Background: Gemcitabine (GEM), a Biopharmaceutical Classification System (BCS) class-III drug, holds promise for non-small cell lung cancer treatment. Utilizing lipid-based nanoparticles for targeted delivery has proven effective in cancer therapy. Biotin receptors, overexpressed in various solid tumors, offer a specific target for enhanced chemotherapy efficacy while minimizing side effects. Hence, this study aimed to formulate biotin-coated Nanostructured Lipid Carriers (NLCs) with Gemcitabine can be delivered to specific tumors by electrostatic attraction.Materials and Methods: Nanostructured Lipid Carrier loaded Gemcitabine was formulated using Oleic acid and Glyceryl monostearate as lipids, with Tetronic 1107 as the surfactant. Formulations were optimized using a 2-factor, 3-level full factorial design approach with Design Expert software. Size of particle, Zeta potential, Polydispersity index, Encapsulation efficiency, Scanning Electron Microscopy, phase contrast microscopy, drug release and in vitrocytotoxicity against A549 cells were assessed for characterization.Results: The optimized Gemcitabine-loaded Nanostructured Lipid Carrier formulation exhibited a particle diameter of 194.5 nanometer (nm) and Biotin-Gemcitabine- Nanostructured Lipid Carrier showed a size of 203.1 nanometer. In vitrodrug release efficiency of about 95.125% during 8 hr for Gemcitabine-Nanostructured Lipid Carrier and 96.04% during 24 hr for Biotin-Gemcitabine-Nanostructured Lipid Carrier, suggesting prolonged circulation for the latter. Cytotoxicity assays revealed significant reduction in cell viability and induction of cytotoxic activity Gemcitabine-loaded Nanostructured Lipid Carrier-biotin at low concentrations in A549 cells.Conclusion: The developed biotin coated Nanostructured Lipid Carrier present a promising strategy for targeted delivery of Gemcitabine to Non-Small Cell Lung Cancer (NSCLC). These nanocarriers could provide a targeted and efficient delivery platform to tumor cells. Further in vivoinvestigations are warranted to validate their safety and therapeutic effectiveness.

Keywords: Gemcitabine; Nanostructured lipid carriers; Biotin coating; Targeted delivery; NSCLC; Cytotoxicity; In vitro release