Nanoencapsulation of Phthalate from Melastomastrum Capitatum (Fern.) in Chitosan-Nps as a Target Mediated Drug Delivery for Multi-Drug Resistant Pathogen

Background: Chitosan nanoparticle (chitosan-NPs) is a polymer obtained from the exoskeletons of crustaceans, and has been applied recently as a carrier for many drug agents. Multi-drug resistance has been the major set-back in the treatment of microbial infections globally. Methods: Dibutyl phthalate (DBP) isolated from Melastomastrum capitatum leaves was encapsulated in chitosan-NPs and its antimicrobial activity was evaluated on selected multi-drug resistant pathogens. The isolated phthalate was characterized by FTIR, NMR and GC-MS. Chitosan-NPs encapsulated phthalate was prepared by ionic gelation of glutaraldehyde cross-linker. Antimicrobial activity of nano encapsulated drugs was carried by agar well diffusion at 0.5 µg/mL concentration. In vivo activity of nano encapsulated drugs were determined in thirty Swiss albino rats weighing 100-150g. Chitosan-NPs encapsulated treatment groups were administered at 0.5 µg/mL (i.p.) as compared with ciprofloxacin positive control group at 2.5 µg/mL. Results: Chitosan-NPs encapsulated phthalate showed the strongest zones of inhibition against VRE ATCC 29212, MRSA NCTC 13435, Candida albicans ATCC 19231, and Clostridiodes difficile NCTC14385. Significant inhibition of bacterial growths was achieved by CSDBP encapsulated phthalate both in vitro and in vivo studies due to low concentrations in ALT, ALP, AST and creatinine, and high volume of WBC in rats. Non-Fickian drug release was observed by the formulations. Conclusion: The study showed that chitosan-NPs mediated drug delivery exhibited strong antimicrobial activity with sustained release against multi-drug microbes in this study. This is promising, and can be employed as mediation for multi-drug resistant pathogens.