Preparation Of Thermo-sensitive Chitosan-based Drug Carriers And Its Study Of Sustained Release Property

Chitosan,as a natural amino polysaccharide with excellent biological properties and reactivity,has great potential for the development and design of drug carriers in the field of drug delivery.The continuous development of drug dosage forms has accelerated the update of drug carriers.It becomes important to design a drug carrier that is more effective and has the ability to target diseased areas in the body.On-demand drug delivery is becoming feasible through the design of stimuli-responsive drug carriers that recognize diseased micro-environment and react in a dynamic way,also have excellent space,time and dose controlled specific drug release performance.As a commonly used design strategy,thermo-sensitive drug carriers currently have broad application prospects in the field of drug delivery.Herein,a thermo-sensitive grafted-chitosan(MCS-g-PNIPAAm)was designed and synthesized by a simple and efficient method,which protected the amino groups on chitosan from interference.The thermo-sensitive chitosan drug-loaded microspheres(MCS-g-PNIPAAm/OSA@BSA MPs)and nanoparticles(MCS-g-PNIPAAm/TPP@BSA NPs)were prepared by emulsion cross-linking method and ionic gelation method used the cross-linking agents oxidized sodium alginate(OSA)and sodium tripolyphosphate(TPP),respectively.The chemical structures were characterized by ~1H NMR and FTIR.The low critical solution temperature(LCST)was measured by temperature-controlled UV-vis,which demonstrated their thermo-sensitive phase transition behavior.Characterized by FE-SEM and DLS,the microspheres and nanoparticles were spherical and the particle size were increased while temperature rises above the LCST.The optimal dose of microspheres and nanoparticles was determined by measuring the drug loading and encapsulation efficiency at different dosages by UV-vis.As the amount of BSA increased,the drug loading gradually increased and the encapsulation efficiency decreased.In vitro drug release experiments show that both microspheres and nanoparticles have excellent thermo-sensitive drug release properties.The kinetics fitting of the drug release data revealed that the drug release in the drug-loaded microspheres obeys the Korsmeyer-Peppas model.The drug release follows the mechanism of diffusion synergistic with corrosion of the polymer matrix at 25?,at 38?follows the Fick diffusion mechanism.The drug release from drug-loaded nanoparticles obeyed the Korsmeyer-Peppas model at 25?,followed the Fick diffusion mechanism,and obeyed the Gompertz model at 40?,that drug releases increases rapidly at the beginning and then slowly released into solution through diffusion control until gradual to maximum dissolution.