Article

Nasal Administration of Dolutegravir Loaded Nanoparticles Based Mucoadhesive in situ Gel: Design and in vivo Assessment

Nagaraja Sreeharsha1,2★, Sandhyanjali Cherukuri3, Nimbagal Raghavendra Naveen3, Prakash Goudanavar3★, Santosh Fattepur4, Bandar Aldhubiab1, Rashed M Almuqbil1, Anroop B Nair1★ Corresponding author

  1. 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.
  2. 2Department of Pharmaceutics, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore, Karnataka, INDIA.
  3. 3Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagar, Karnataka, INDIA.
  4. 4School of Pharmacy, Management and Science University, Seksyen, Shah Alam, Selangor, MALAYSIA.

CORRESPONDENCE

Nagaraja Sreeharsha

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, SAUDI ARABIA.

pgoudanavar01@gmail.com

Received: 12-07-2023; Revised: 26-10-2023; Accepted: 30-12-2023.

Volume 58, Issue 2 · pp. 470–479 · PUBLISHED 2024 · DOI: 10.5530/ijper.58.2.41

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ABSTRACT

Background: To assess the potential for targeting the brain through intranasal delivery, this study focuses on optimizing and developing a mucoadhesive in situ gel formulation containing Dolutegravir nanoparticles. Materials and Methods: Employing a central composite design, the study optimized the concentration of variables of Hydroxypropyl methylcellulose (HPMC, X1) and Poloxamer 407 (X2) on the gelation temperature (Y1) and drug release (Y2). The optimized drug loaded nanoformulations were assessed for various pharmaceutical features, in vitro release and evaluated in vivo. Results: Both variables significantly impacted the responses (p<0.05). The selected formulation displayed beneficial rheological characteristics and prolonged drug release. In vivo pharmacokinetic analysis in rats post-intranasal administration of the optimized in situ gel demonstrated markedly higher (p<0.0001) Cmax (2-fold) and AUC0-t (3-fold) values in the targeted brain tissue as compared to intravenous administration. Reduced Dolutegravir exposure in the central compartment validates limited absorption with nasal therapy. Conclusion: The study affirms the potential of the in situ mucoadhesive nasal gel in delivering Dolutegravir to the brain. Thus, the optimized nasal gel emerges as a promising therapeutic alternative for Neuro AIDS by efficiently delivering Dolutegravir to the brain.

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    Sreeharsha, N., Cherukuri, S., Naveen, N. R., Goudanavar, P., Fattepur, S., Aldhubiab, B., Almuqbil, R. M., & Nair, A. B. (2024). Nasal Administration of Dolutegravir Loaded Nanoparticles Based Mucoadhesive in situ Gel: Design and in vivo Assessment. Indian Journal of Pharmaceutical Education and Research, 58(2), 470–479. https://doi.org/10.5530/ijper.58.2.41