Effects of chitosan on the performance of heparin microcapsule
- VernacularTitle:壳聚糖对肝素微胶囊性能的影响
- Author:
Shan DING
;
Lihua LI
;
Changren ZHOU
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2006;10(33):-
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Chitosan and sodium alginate are the good natural materials for microcapsule, and also used widely in tissue engineering. Our research teams have made thorough work at anticoagulant materials, but these materials are inert or simulate the liquid crYstal form of blood vessel wall. While in this experiment, on the base of our previous study, we microencapsulated heparin with biotic anticoagulation activity and other specific performances in order to enable microcapsule to have a long time releasing effect of medicine.OBJECTIVE: To microencapsulate the low molecular heparin so as to ensure the stability of heparin in vivo and analyze the effect of content of chitosan on the performance of heparin microcapsules basing on the natural chitosan and sodium alginate as the enwrapped materials of microcapsules.DESIGN: Open experiment.SETTING: Department of Material Science and Engineering, Jinan University.MATERIALS: The experiment was performed at the laboratory of Department of Material Science and Engineering, Jinan University from October 2004 to June 2005. Heparin, with relative molecular mass＜ 5 000, was provided by Shandong Freda Biochem Co., Ltd.,; Chitosan was provided by Shanghai Bio Life Science & Technology Co., Ltd, DD≥90%, η＜ 100 cps;Sodium alginate was provided by Qingdao Bright Moon Seaweed Industrial Co., Ltd. Emulsions were Span80, and CaCl2, which were both made in China.METHODS: ①Preparation of heparin/chitosan microcapsules (HCM):Some heparin aqueous solution was emulsified in liquid paraffin. The reaction system was stirred fully and presented emulsion. Then the whole reaction system was warmed to be at 50 ℃ and maintained for 20 minutes. Afterwards, 20 g/L chitosan solution was added slowly, subsequently with raising the temperature to be at 60 ℃ and then glutaraldehyde was dropwised keeping the reaction system at 80 ℃ for 1hour. Centrifugation, filtration and washing followed by washing with kerosene fully, remain organic was extracted by dehydrated alcohol with extractor were performed.Drying and xeransis in vacuum were done at last. ② Preparation of heparin-sodium alginate-chitosan microcapsules (HSCM) :Heparin aqueous solution and sodium alginate were emulsified in paraffin, and the reaction system was stirred into emulsion at room temperature for 20 minutes, then 3% CaCl2 solution containing different concentrations of chitosan was added slowly. 30 minutes later, Microcapsules were separated, washed and dried as the treatments as before. ③ Drug content and envelope efficiency were measured, heparin standard curve was determined and in vitro releasing effect of heparin microcapsules was also measured.MAIN OUTCOME MEASURES: ①Effect of chitosan solution concentration on preparation of heparin-chitosan microcapsules; ② Effect of glutaraldehyde dosage on preparation of heparin-chitosan microcapsules; ③Effect of sodium alginate concentration on hepatin-sodium alginate; ④Effect of chitosan concentration on hepatin-sodium alginate-chitosan microcapsules. ⑤ In vitro release of heparin microcapsules enwrapped by different materials. ⑥Measurement of heparin content and envelope efficiency. ⑦ Observation of heparin microcapsule under scanning electron microscope RESULTS: ①With the increasing concentration of chitosan, the color of production changed from yellow to dark, and microcapsules were increscent, but the microcapsules uniformity and property of balling were increased. ②The increasing content of glutaraldehyde led darker production.Increase of glutaraldehyde content made production bond each other severely. The glutaraldehyde, which did not react with chitosan, can solidify itself and presented anomalous microcapsules forming. ③There was not obvious balling property of the production with the change of concentration of sodium alginate. ④The balling property of microsphere was good with increasing concentration of chitosan. However, microcapsules conglutinated with each other. 2% chitosan would be better. ⑤With the increase of chitosan content, the releasing speed ofheparin became slow. ⑥The envelope efficiency was about 58% when microcapsule contained 20%(wt) of chitosan, and used chitosan only the envelope efficiency could approach to 79.9%. ⑦ The surface of microcapsules with chitosan was very compact,and with increasing of content of glutaraldehyde, microcapsules would bond each other.CONCLUSION: Chitosan at certain concentration will affect the uniformity and balling property of microcapsules. Chitosan dosage can alter the envelope efficiency of heparin. Envelope efficiency of heparin is increased and releasing speed of heparin is decreased with the increase of content of chitosan.
