Three dimensional polymeric networks based on poly(methacrylic acid) and protein for targeted delivery of poorly water-soluble drugs

Abstract

Three dimensional polymer networks, hydrogels, have shown a great potential in controlled release and targeted delivery of active substances. pH sensitive hydrogels based on poly(methacrylic acid) have attracted significant attention due to their biocompatibility, non-toxicity and the possession of the huge number of ionogenic carboxylic groups. On the other hand, the usage of these hydrogels for controlled release and targeted delivery of poorly water-soluble drugs is limited by their highly hydrophilic nature. We overcame this limitation by modifying PMAA with amphiphilic substance - casein. The addition of this natural protein enabled the encapsulation, targeted delivery and controlled release of poorly water-soluble model drug - caffeine. Three carriers with different neutralization degree of methacrylic acid were synthesized via free radical polymerization. The FTIR spectra revealed that two types of interactions were established between casein and caffeine: hydrophobic interactions and hydrogen bonds. The SEM micrographs showed that the structure of the carriers depended on the change of neutralization degree of the methacrylic acid. The swelling of synthesized carriers and the caffeine in vitro release were monitored in two environments at 37°C: 0.1M HCl pH=1.2 (simulation of environment in human stomach) and phosphate buffer pH=6.8 (simulation of environment in human intestines). The synthesized carriers had higher swelling degree and the higher release rate of caffeine in the phosphate buffer pH=6.8 than in 0.1M HCl. The increase in neutralization degree of methacrylic acid caused the increase in swelling degree of the carriers and the increase in release rate of caffeine. Presented results showed that synthesized carriers are promising candidates for targeted delivery of poorly water-soluble drugs.