In Vivo Pharmacokinetic and Histopathological Evaluation of Ritonavir-Loaded Polymeric Micelles
Keywords:
Ritonavir, Polymeric micelles, PEG-PCL, Oral bioavailability, Factorial design, Nanocarriers, Drug delivery, Pharmacokinetics, In vivo study, HistopathologyAbstract
The study aimed to enhance the oral bioavailability of Ritonavir (RTV), a poorly soluble antiretroviral drug, through the development of polymeric micelles (PMs) using poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as a biodegradable copolymer. A 3² factorial design was employed to optimize formulation parameters, including drug-to-polymer ratio and sonication time, to achieve desirable particle size and encapsulation efficiency. The optimized micelles were prepared via the thin-film hydration method and characterized for physicochemical properties, in vitro drug release, and in vivo pharmacokinetics. The optimized RTV-PMs demonstrated nanosized uniform micelles with high encapsulation efficiency and sustained drug release. In vivo pharmacokinetic evaluation in rats revealed a 3.8-fold increase in bioavailability compared to pure drug suspension, confirming improved systemic exposure. Histopathological analysis of gastrointestinal tissues showed no signs of inflammation or damage, confirming the formulation’s safety. Overall, the developed PEG-PCL-based micellar system successfully improved the solubility, absorption, and oral bioavailability of Ritonavir, offering a promising and patient-friendly alternative for enhanced antiretroviral therapy.
