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Preparation and Properties of Chitosan-based Thermosensitive Composite Hydrogel

Author: YuTao
Tutor: LiHePing
School: Changsha University of Science and Technology
Course: Organic Chemistry
Keywords: Chitosan Carboxyethyl Folic acid Temperature -sensitive hydrogel pH sensitivity of Drug carrier Sustained-release
CLC: R943
Type: Master's thesis
Year: 2011
Downloads: 15
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Abstract

Some new type chitosan-based thermosensitive hydrogels were designed and synthesized with folic acid or N-carboxyethyl modified,we used 5-fluorouracil as model drug and constructed the drug sustained releasing systems, then studied their releasing behavior. The main contents of this thesis as following:(1) Two series of novel chitosan-based thermosensitive hydrogel drug carriers were designed and synthesized. They were: N-carboxyethyl modified chitosan- based thermosensitive hydrogel, including ACS/FuH which loaded drug by hydrogel-entrapping, ACSFuH which loaded drug by chemical-bonding, and ACSCH prepared by both chemical-bonding and hydrogel-entrapping; folic acid modified chitosan-based thermosensitive hydrogel, including FACS/FuH prepared by folic acid modified chitosan, CS/FAFuH and ACS/FAFuH synthesized by folic acid modified 5- fluorouracil. A total of six new hydrogels were obtained, and their structures were characterized by IR, UV-Vis or LC/MS.(2) Discussed the best optimum conditions of N-carboxyethyl chitosan and its hydrogel. When the feeding of acrylic acid and chitosan ratio was 2.0 ml/0.1 g and the reaction temperature is 60℃, ACS could easily obtained by microwave heating only for 1 h in a grafting yield of 52.97%, which was proved to be a faster and more efficient way than the ordinary methods. The experiment also confirmed that the reactive amino in hydrogel, pH and temperature of solution could affect the change of sol-gel, N-carboxyethyl chitosan-based hydrogel could changed into gel at 37℃for 25 min when the pH of solution was 7.(3) The drug loading and releasing properties in vitro of drug sustained releasing systems of series N-carboxyethyl were determined with UV-Vis. ACS/FuH had highest drug loading in series N-carboxyethyl, the drug loading was 50% and encapsulation efficiency was 100%. But it effect of releasing was bad, the cumulative release rate of ACS/FuH was 64.68% in the first 3 h with a slight burst releasing, and reached 78.80% at 8h, the complete releasing happened in 15 h, showing a relatively fast releasing. ACSFuH had the best releasing effect, the cumulative release rate was 43.52% in the first 8 h, and 94.76% in 7 d, and however its drug loading was only 17.26%. ACSCH had both excellent releasing effect and high drug loading, its drug loading was 29.44% and encapsulation efficiency was 33.84%. The cumulative release rate of ACSCH was 48.25% in the first 3 h and 60.16% in 8 h without apparent burst releasing, in addition the drug loading and release effect of ACSCH could be adjusted according to the actual situation.(4) In series folic acid modified, FACS/FuH had the highest drug loading, the maximum of the amount of contained 5-Fu only be determined via its solubility in the solution. Although CS/FAFuH and ACS/FAFuH were loaded drug by hydrogel-entrapping, but as the solubility of 5-Fu-FA was very poor, we couldn’t obtained the products which had high drug loading, the drug loading of them were 10.73%. We found that the diffusion rate would be slower when 5-fluorouracil was modified by folic acid, and ACS/FAFuH had pH sensitivity, it could Swelling in the PBS buffer which pH was 7.4, in this environment its cumulative release rate was 73.2% in 8h and more suitable as a drug carrier.

Preparation and Properties of Chitosan-based Thermosensitive Composite Hydrogel

Abstract

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