Design Evaluation and Optimization of Novel Lipid Based Nanostructured Formulations for Enhancement of Oral Bioavailability of Dolutegravir

Abstract

The oral delivery of Dolutegravir is limited by poor aqueous solubility and variable bioavailability, reducing therapeutic efficacy in long-term antiretroviral therapy. This study aimed to design, evaluate, and optimize lipid-based nanostructured formulations to enhance the oral bioavailability of Dolutegravir. Dolutegravir-loaded nanostructured lipid carriers (DNLCs) were prepared using a modified emulsification–evaporation method followed by low-temperature solidification. Nine formulations (DNLC1–DNLC9) were developed by varying lipid and surfactant concentrations and characterized for particle size, zeta potential, entrapment efficiency, morphology, in vitro drug release, release kinetics, and stability. The DNLCs exhibited nanoscale particle size, good entrapment efficiency, and adequate surface charge, indicating colloidal stability. DNLC5 was identified as the optimized formulation, showing the smallest particle size (121 ± 8.14 nm), highest entrapment efficiency (88 ± 1.74%), and favorable zeta potential (–22.5 mV). SEM confirmed spherical, uniformly distributed nanoparticles with minimal aggregation. In vitro drug release studies demonstrated sustained release over 24 hours, with DNLC5 achieving nearly complete drug release (99.04%). Release kinetics indicated diffusion-controlled mechanisms with near Zero-order release for DNLC5. Stability studies under accelerated conditions confirmed formulation stability for up to 180 days. Overall, lipid-based nanostructured carriers represent a promising strategy to enhance the oral bioavailability of Dolutegravir, with DNLC5 offering sustained delivery, reduced dosing frequency, and improved patient compliance.