Oral Administration of Eudragit Coated Bromelain Encapsulated PLGA Nanoparticles for Effective Delivery of Bromelain for Chemotherapy in vivo

Bromelain, a proteolytic enzyme, is widely used as a chemo preventive agent against human cancers. As proteins are susceptible to denaturation at acidic pH when given orally, it results in low bioavailability. Therefore, bromelain encapsulated poly (lactide-co-glycolic) acid nanoparticles, BR-PLGA were formulated and coated with acidic pH resistive polymer, Eudragit, in order to provide stability against degradation in the acidic pH. Physiochemical characterization of particles was carried out. The proteolytic activity and the structure integrity of bromelain after encapsulation were calculated. The release kinetics was also evaluated to explain the mechanism of drug release. A comparative study involving BR-PLGA and free bromelain was done to demonstrate their antitumor efficacy in vitro and in vivo. The particles (145.6±9.85nm) were prepared with 48±4.81% entrapment efficiency. Mathematical analysis of the release kinetics indicated that bromelain release followed Higuchi release model. Also, the coated nanoparticles showed ~40% reduction in burst release at acidic pH (~1.5). Further, the particles were found to be stable in various simulated GIT media. In-vitro chemo sensitivity assay revealed ~7-10 folds reduction in IC₅₀. These results were also corroborated by in vivo observations. Eudragit coated Bromelain loaded nanoparticles could be a promising delivery system for cancer treatment.