Preparetion And Drug Release Research Of PH-responsive PEGylated Chitosan-based Nanomicelle

Chitosan and poly(ethylene glycol) are widely used in biomedical field. Theyhave good biodegradability, biocompatibility and low toxicity. Our group haveprepared self-assembled N,N-dialkyl chitosan (DACS). Based on DACS, a new typeof PEGylated chitosan derivative was synthesized in order to prepare the stealthnano-micelles for application in the drug delivery system.Through the acylation reaction, a series of novel chitosan amphiphilicderivatives N,N-dialkyl-3,6-O-mPEG-chitosan (PEDACS) with high degree ofgrafting was synthesized by grafting mPEG-COOH onto N,N-dilauryl chitosan. Inaddition, the alkyl chains were octyl, decyl and lauryl respectively. And the molecularweight of mPEG was500and1000Da separately. The products were characteredthrough the methods of1H NMR, FTIR, EA and so on.The experimental results showed that the degree of alkyl and mPEG substitutionwas about1.90and1.60respectively in the products. The Critical micelleconcentration (CMC) of the products was determined by steady-state fluorescencemethod. The CMC value of the products would be decreased with the chain ofN,N-dialkyl increasing and the molecular weight of mPEG raising. Because the poorwater solubility of PEDLCS-500, PEDLCS-1000was better for further study. TheCMC value of PEDLCS-1000was0.1170mg mL-1. The drug loading concent andefficiency of KP-loaded PEDLCS micelles was determined as34.48%and65.78%respectively under the optimal ratio of KP and PEDLCS-1000(0.8:1). And theKP-loaded PEDLCS micelles had an average size of155.1nm and zeta potential of-31.6mV. The same phenomenons appeared in two different simulated body fluidswith different pH. The stability of the micelles decreased and diameter of the micellesincreased with the reduction of the pH value. When the pH value varied from7.4and6.5to5.5, the micelles could be changed from transparent to flocculation, and theprocess was reversible. The drug release behaviour of drug-loaded micelles wasexamined at pH6.5and7.4simulated body fluid separately. It showed the release behavior of drug-loaded micelles had a certain pH sensitivity.PEDACS could form the smaller stealth micelles which achieved thelong-circulating of body. And the range of pH response was rightly fit to the growthmicroenvironment of tumor cell (pH7.2～6.0). It would be expected to become anew material of drug delivery system.