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

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, X 1 ) and Poloxamer 407 (X 2 ) on the gelation temperature (Y 1 ) and drug release (Y 2 ). 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) C max (2-fold) and AUC 0-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.

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

“…The significance of biopolymer NPs has demonstrated a higher capacity to deliver medicine to the CNS and to enhance its pharmacological action of actives by nose-to-brain delivery was also reported [ 74 ]. Drug molecules including carboplatin, carmustine, diazepam, lorazepam, lurasidone, dolutegravir, and oxcarbazepine have been assessed by developing PNs for brain delivery by intranasal route [ 106 , 107 , 108 ]. Biodegradable and biocompatible polymers including chitosan, polycaprolactone, polylactic acid, and PLGA (poly lactic-co-glycolic acid), which are approved by the US FDA, were widely utilized in developing PNs aimed for intranasal delivery [ 109 ].…”