Development and Evaluation of Polymeric Micelles for Solubilization and Enhanced Oral Bioavailability of a Poorly Soluble Anti-HIV Drug (Ritonavir)

Abstract

The present study aimed to develop and evaluate polymeric micelles (PMs) as a nanocarrier system to overcome the poor aqueous solubility and limited oral bioavailability of ritonavir (RTV), a critical anti-HIV drug. Ritonavir-loaded polymeric micelles (RTV-PMs) were prepared using poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) via the thin-film hydration method and optimized through a 3² full factorial design considering drug-to-polymer ratio and sonication time as variables. The optimized RTV-PMs exhibited a mean particle size of 95.6 ± 4.1 nm, narrow size distribution (PDI 0.18 ± 0.02), high encapsulation efficiency (92.4 ± 3.5%), and drug loading of 15.1 ± 1.2%. Transmission electron microscopy confirmed spherical morphology with a distinct core–shell structure. In vitro and in vivo evaluations demonstrated enhanced solubility, improved dissolution rate, and significantly higher oral bioavailability of RTV compared to pure drug. These findings highlight the potential of PEG-PCL-based polymeric micelles as a promising, biocompatible nanocarrier system to address biopharmaceutical challenges associated with ritonavir and improve therapeutic efficacy in HIV treatment.