DoE Based Optimization and Development of Spray-Dried Chitosan-Coated Alginate Microparticles Loaded with Cisplatin for the Treatment of Cervical Cancer.

Abstract

The existing parenteral treatment of cervical cancer has high toxicity and poor distribution of drugs at the targeted site. To formulate localized mucoadhesive cisplatin loaded microparticles based formulation to treat cervical cancer so that enhanced therapeutics benefits with low toxicity could be achieved. Cisplatin loaded chitosan coated spray-dried microparticles were prepared by ionotropic gelation technique and optimized by Central Composite Design. The spray-dried uncoated and chitosan- coated microparticles were characterized for various parameters (Particle size, Morphology, Drug entrapment efficiency). In vitro drug release study was carried out in simulated vaginal fluids by dialysis membrane method. Ex vivo studies were carried out to evaluate the cytotoxic potential of the developed formulation by the MTT assay. A drug permeability study was performed by Franz diffusion cell using the vaginal tissue of Swiss Albino Mice. All in vitro characterization parameters were found to be optimum. The in vitro release studies indicated a controlled release following the Higuchi model. The chitosan-coated microparticles were found to be more cytotoxic than uncoated microparticles and plain cisplatin solution. The chitosan-coated microparticles were found to be more permeable than uncoated microparticles. Finally, in vivo tumor regression and histopathological studies confirmed the significant decrease in tumor volume at different time intervals. Thus, it can be concluded that mucoadhesive spray-dried microparticles could provide a favorable approach for localized delivery of the anticancer drug via vaginal route against cervical cancer with its enhanced effectiveness.