Development of Alginate-Based Nanoparticulate Drug Delivery System for Anti HIV Drug Ritonavir

Ritonavir is an important protease inhibitor for HIV treatment. But this useful drug possesses certain shortcomings i.e. short life as well as side effects. The aim of this study is to improve the therapeutic effect of the drug by altering the delivery system. Slow release ritonavir-loaded nanoparticles in alginate, biodegradable hydropolymer, were prepared by in-situ nanoemulsion-polymer crosslinking approach. Different formulations varying in the drug loading solvent phase were prepared. Four different drug-loading solvents were used. However among them dichloromethane provided maximum load of drug in nanoparticles i.e. 15.203%. Ritonavir loading was confirmed by Fourier Transform Infra-red Spectrophotometer (FT-IR) and quantitated by High Performance Liquid Chromatography (HPLC). Prepared nanoparticles appeared slightly elongated with a dense drug core in transmission electron microscopy studies. Hydrodynamic diameter of nanoparticles was 220 ± 1.7 nm. Sustained diffusive drug release was observed in vitro, depending on drug polymer ratio; alginate nanoparticles are able to deliver 30 to 80% of the loaded drug by the end of 24 hour. The nanoparticles prepared with 1:6 drug polymer ratio show better release pattern and control the drug release over a period of 24 hour. The release followed Higuchi kinetics rather than first order kinetics, indicating diffusion controlled drug release. The nanoparticulation technique developed can be a good choice for the development of different sustained protease inhibitor drug carriers.