Polysaccharide Nanogels for the Delivery of Gemcitabine Hydrochloride

Abstract

The clinical application of gemcitabine is limited by hydrophilicity and low plasma half-life. Herein, we developed a chitosan-based nanogel to provide controlled release of gemcitabine and relieve its hydrophilicity. Moreover, the chitosan nanogel is decorated with an alginate polyanion for pH-dependent and more controlled drug release. The effect of different variables on the polyelectrolyte reaction was evaluated using the Box–Benkehen design. The optimum formulation was determined based on higher encapsulation efficiency and loading capacity using HPLC analysis. In the light of the results, this synthesized nanogel has a diameter of around 150 nm and a polydispersity index of 0.344 and provides an acidic pH-dependent release profile. As a result of retaining the ability of cellular uptake, nanogel-loaded gemcitabine led to the cell cycle and apoptosis induction in MCF-7 breast cancer cells, followed by a considerably decreased half-maximal inhibitory concentration (IC50) of cell proliferation compared to free gemcitabine. Based on these results, the chitosan–alginate nanogel can be applied as a pH-dependent platform for the more controlled release behavior of gemcitabine.

pH-Responsive, Reactive Oxygen Species Scavenging and Highly Swellable Nanogel for Colon-Targeted Oral Drug Delivery

“…At the elevated pH, deprotonation of such carboxylic acid groups tends to accumulate higher amounts of superficial negative charges. This leads to electrostatic repulsion among these negatively charged groups and promotes swelling of the nanogels . On the other hand, in acidic pH conditions, amine groups become protonated.…”

“…This leads to electrostatic repulsion among these negatively charged groups and promotes swelling of the nanogels. 73 On the other hand, in acidic pH conditions, amine groups become protonated. However, these protonated functional groups form hydrogen bonds with the counterions within the nanogels which limits their swelling.…”