Construction And Biological Evaluation Of Temperature Sensitive Hydrogel Drug Delivery System

The studies to overcome cancers should be without delay! With the progress of nanotechnology,nano-drug delivery system has become the focus of new drug pharmaceutics.Nano-drug delivery system can not only improve the solubility of drugs,improve the pharmacokinetic properties,and change the way and route of drug transmission.It can also prolong the time of drug action and achieve targeted therapy to improve drug efficacy and reduce side effects simultaneously.However,the efficacy of the anticancer drug delivery system in the treatment of solid tumors is still not satisfactory.The bioavailability and therapeutic effect still need to be improved,which is also become the key problem to be solved in nano-drug delivery system.During studies of nano-drug delivery systems,hydrogels are widely used to achieve drug delivery and controlled release.Because of their good biocompatibility and hydrophilicity,nano hydrogels are one of the most advanced drug carriers.Furthermore,among all nano hydrogels,thermosensitive hydrogels are the most intelligent hydrogels currently studied and developed,and have been widely used in nano-drug delivery systems.Thermosensitive hydrogels are a class of polymers that can respond to temperature.Their phase transition temperature(LCST)could be close to the body temperature,and can also be adjusted according to application requirements.In this study,a novel hydrogel nanoparticle drug delivery system was constructed.This system was expected for delivery and controlled release of chemotherapeutic drugs.In addition,we considered application of assistant in the system,hoping to improve the bioavailability of the drug.Through using N-Isopropyl acrylamide(NIPAM)and acrylic acid(AA)monomers as main raw materials,using methylene-bis-acrylamide(BIS)as crosslinking agent and ammonium persulphate(APS)as initiator,a biocompatible and injectable hydrogel drug carrier was obtained by polymerization reaction.This drug carrier simultaneously contained anticancer drugs and assistants.Furthermore,the temperature sensitivity of this carrier with different monomer ratios was investigated.The structure and composition were characterized by Fourier transform infrared spectroscopy(FTIR).The morphology and particle size were characterized by scanning electron microscopy(SEM)and dynamic light scattering(DLS),respectively.The drug loading and drug release were investigated.The cytotoxicity and efficacy were studied in vitro.Anti-tumor activity and distribution within the tissue were studied through nude mouse tumorigenicity assay.The results showed that the hydrogel particles were uniform in size and low in viscosity.The drug release was fast.At the same time,with the increase of the proportion of AA,the LCST of hydrogel was increased.In vitro experiments showed that the combination of assistants and chemotherapy drugs effectively improved the anti-tumor effect and reduce drug resistance.In vivo experiments have shown that simultaneous delivery of drugs and assistants with nano-drug delivery system significantly inhibited nude mice tumor growth.In all,the system has a significant advantage in improving the bioavailability of the drug,achieves synergistic effect of drugs and ssistants,and ultimately improves the treatment of the tumor.