Release of paclitaxel from pH sensitive and biodegradable dextran based hydrogels

Abstract

Two different dextran based pH sensitive and enzyme degradable hydrogels: dextran maleic acid (Dex-MA), and glycidyl methacrylated dextran (Dex-GMA) were synthesized for oral delivery of nanoparticles. Poorly water soluble drug paclitaxel nanoparticles (PAX NPs) were prepared as the model, and encapsulation efficiency of paclitaxel in the nanoparticles was optimized to 43%. The prepared hydrogels were stable in simulated gastric fluid, but were prone to swelling and degradation in the presence or absence of enzyme dextranase in simulated intestinal fluid. Release profiles of nanoparticles could be tuned from 5.5 h to as long as 24 h under simulated human GI conditions. The release of PAX NPs (110 ± 10 nm) was completed with longer time (45 h–120 h). Two possible release mechanisms were discussed for Dex-MA and Dex-GMA-co-AA hydrogels respectively: degradation controlled, and diffusion controlled. These two biodegradable hydrogels, which can release nanoparticles depending on pH changes, may be suitable as potential colon targeting vehicles for oral delivery of drug nanoparticles.