Research On Preparation And Controlled Release Of Modified Chitosan Nanoparticles

The rapid development of modern biotechnology brings about many protein and peptide drugs, which are degradable by proteolytic enzyme in intestinal and not oral. Moreover, most protein and peptide drugs are hard through the biological barrier, resulting in low bioavailability, and only can be used by injection and perfusion. The most drugs release quickly after administrated, which brings the drug level increases rapidly and decreases after reaching the peak. For drugs, the effect is closely related to the concentrations in serum. So the fluctuation of concentration leads to unaccepted side-effect at the peak, and inadequate treating effect at low drug concentrations. Drug delivery system is catering to said problems, and becoming an important developing in drug field recently, so the selecting and researching of drug carriers or delivery materials become a research focus. The delivery materials with extensive sources, poisonless and harmless, and high encapsulation efficiency are pursued by people.In this paper, the delivery material of hydroxypropyl-chitosan was prepared by hydrophilic modification of chitosan, basing on researches for the condition of forming chitosan particles and the effect of drug delivery. Then by coupling folate which has the target effect of tumor to hydroxypropyl-chitosan, the folate-hydroxypropyl-chitosan was prepared and the drug delivery result of folate-hydroxypropyl-chitosan particles was studied. The major contents and results include:1. The chitosan nanoparticle was prepared by ion gel. The condition of chitosan forming sphere was determined and the nanoparticle was characterized by TEM. The results of encapsulation and delivery were studied by taking bovine serum albumin (BSA) as model drug. The results showed that the BSA encapsulation efficiency and the BSA loading were affected by the initial CS concentration and the initial BSA concentration. The higher was the initial chitosan concentration, the higher the BSA encapsulation efficiency and the BSA loading. However, it showed opposite trend when the initial BSA concentration increased. The highest encapsulation efficiency and loading of BSA reached 86% and 49%, respectively. The behavior of chitosan nanoparticles for BSA in vitro release reveals a controlled and continuous release of the entrapped protein after 12 hours and releases 30% of the BSA loading within 2 hours.2. By the reaction of propylene oxide and chitosan under alkaline condition that introducing hydroxypropyl to chitosan, the water-soluble hydroxypropyl-chitosan (HCS) was prepared. The synthesis of hydroxypropyl-chitosan was determined by Fourier Transform Infrared Spectroscope. The hydroxypropyl-chitosan particles were observed by TEM, and the effect of encapsulation and delivery was also researched. The results suggested that the prepared hydroxypropyl-chitosan particle was characterized by regular sphere, uniform distribution of particle size, high encapsulation efficiency, high drug loading and good delivery, and the highest encapsulation efficiency and loading of BSA reached 86% and 46%, respectively. The behavior of HCS nanoparticles releases 28% in average within 2 hours and reveals a continuous release of the entrapped protein.3. The folate-hydroxypropyl-chitosan (FHCS) was prepared by the folate coupled to hydroxypropyl-chitosan under the condition of neutral aqueous solution and dark environment. The effects of temperature, concentrations and time on FHCS yield were studied. The result suggested that the optimal values of content, time and temperature were FHCS 2.0mg/ml, folate 120μg/ml, 70min and 80℃, respectively. The highest yield is 31.3%. Then the folate-hydroxypropyl-chitosan particles was prepared by ion gel, characterized by TEM,and meanwhile, the effect of encapsulation and delivery were researched. The results showed that the prepared folate-hydroxypropyl-chitosan particle had advantages of regular sphere, uniform distribution of particle size. And the highest encapsulation efficiency and loading of BSA reached 90% and 48%, respectively. The FHCS nanoparticles releases 26% in average within 2 hours and reveals a continuous release of the entrapped protein.