Studies On The Preparation And Drug Controllled Release Of PH And Reduction Responsive Chitosan Nanogels

The study on intelligent drug delivery systems and their applications is an interesting topic of medical materials. Chitosan(CS) is the only positively charged polysaccharide exited in nature. It has wide applications in biomedical field due to its good biocompatibility, biodegradability, low toxicity and other characteristics. In this paper, CS and its derivative carboxymethyl chitosan(CMCS) were used to prepare nanogels with p H and reduction dual sensitivies. The nanogels were used as anti cancer drug carries to study controlled release performance in order to increase drug uptake in the tumor cells and reduce drug side effects.The main contents are described as follow:N,N-bis(3-carboxy-acryloyl) cystamine(BCCy) containing disulfide bonds was synthesized and CS nanogels were prepared using BCCy as a crosslinker, reacting in the presence of EDC/NHS in aqueous solution. The effects of p H and reduction environment on nanogels were studied. As a model drug, camptothecin(CPT) was loaded on the nanogels for investigating controlled release. Cytotoxicities of blank and drug-loaded nanogels were tested. Results showed that the particle size decreased as the amount of crosslinking agent increased. The nanogels had good biocompatibility,significant p H and reduction sensitivities. The drug loading and encapsulation efficiency of the nanogels can reach 14.16% and 70.80% respectively, and the in vitro release revealed that the nanogels have significant p H and reduction sensitivities.Methacrylamide carboxymethyl chitosan(MC) with side group containing carbon-carbon double bonds was synthesized through the reaction of CMCS with methacrylic anhydride. Negatively charged nanogels were prepared by free radical polymerization of MC and N,N-Bis(acryloyl)cystamine(BACy). The effects of p H and reduction environment on nanogels were studied. Anti-protein performance of nanogels was also tested. Doxorubicin hydrochloride was loaded on the nanogels through electrostatic interaction for investigating controlled release. Cytotoxicities of blank and drug-loaded nanogels were tested. Results showed that the particle size decreased as the substitution degree of MC increased. The nanogels had good biocompatibility, significant p H and reduction sensitivities and could prevent protein adsorption. The drug loading and encapsulation efficiency of the nanogels can reach 18.17% and 90.86% respectively, and the in vitro release showed significant salt, p H and reduction sensitivities.The nanogels have obvious advantages such as simple preparation process,free of organic solvents, size controllable, biocompatible,and environmental sensitivity. They can be potentially used as drug delevery vehicles for p H and reduction stimuli controlled release, so as to enhance the drug uptake by tumor cells, improve the bioavailability and reduce the toxicity of the drug.