Evaluation the performance of polysaccharide base hydrogels in drug delivery of Gemcitabine hydrochloride in the treatment of breast cancer

Gemcitabine (۲', ۲'-difluoro-۲'-deoxycytidine) is a chemotherapeutic agent against human cancers. However, the therapeutic efficacy of gemcitabine is limited by its hydrophilicity and low plasma half-life. To improve the maintaining and efficacy of gemcitabine, we developed a pH sensitive hydrogel drug delivery system based on natural polysaccharides including chitosan and alginate. To optimize the hydrogel preparation procedure, the effect of critical parameters on the physicochemical characteristics of nanoparticles was investigated through the Box-Benkehen design. Finally, optimized formulation resulted in stable NPs around ۱۴.۹۶ nm by polydispersity index ۰.۲۲۵ and a maximum entrapment efficiency of ۳۴.۱۱%. The in vitro release studies have shown that in the presence of the alginate layer, the burst release is reduced under different pH conditions and ~۸۰% of gemcitabine hydrochloride was released within ۴h. Based on the results of the cell cytotoxicity the drug-loaded NPs showed increased toxicity over human breast cancer cells (MCF-۷). The flow cytometry results suggest that the prepared NP can induce apoptosis more effectively than free gemcitabine hydrochloride. Moreover, cell-cycle analysis indicated that G۲/M arrest, also the results of cell uptake studies represented the time-dependent increasing behavior which can be evidence for the developing pH-responsive and time-dependent drug delivery systems based on CS-AL polyelectrolyte complex. So to sum up, the assembled nature polymeric core-shell system not only provides the pH sensitivity and improved biocompatibility hydrogel but also enables protecting Gemcitabine hydrochloride from enzymatic degradation.

Keywords:

Chitosan , Alginate , drug delivery , pH-sensitive system