Interaction of lectin-conjugated bioadhesive microparticles with mucin and their application to oral insulin delivery system = 생체접착성 마이크로입자와 mucin의 상호작용과 경구 투여 인슐린 제제에 응용하는 연구

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Bioadhesive microparticles conjugated with lectin (wheat germ agglutinin, WGA) were prepared as biodegradable polymeric carriers for oral delivery of insulin. Their specific interaction with mucin was determined by pig mucin (PM) immobilized surface plasmon resonance (SPR) biosensor, in vitro studies with mucin solution and in vivo studies with diabetic rats. Stimuli-sensitive systems which respond to temperature, electricity and pH were prepared for the preliminary studies of oral peptide delivery. Soluble starch-g-PAA (SGPAA) was synthesized to prepare biodegradable material. SGPAA microparticles were prepared by an emulsion-precipitation method using a W/O emulsion. The WGA was conjugated to carboxylic groups of microparticles by the carbodiimide/N-hydroxysuccinimide technique. The pig mucin (PM) was attached to the gold surface of SPR sensor. As the SGPAA-WGA microparticles interact with a mucin layer of SPR sensor, the large shift of refractive index was observed and its affinity constant was $K=2.162g^{-1}L$, which is greater than that of SGPAA microparticles ($K=0.162g^{-1}L$). In vitro experiments in a pig mucin solution showed that the SGPAA-WGA microparticles interacted about 8 times greater than the SGPAA microparticles. The thermo-sensitive polymer, PNIPAM-grafted ethylcellulose was synthesized and confirmed by FTIR spectroscopy. Microparticles were prepared by spray drying method using B-191 Mini Spray Dryer. The release rate of allopurinol (model drug) from ECGPN8 microparticles was slower at 40℃(above the LCST) than that of 25℃(below the LCST) probably due to the collapse of PNIPAM chains by temperature. Although PNIPAM took the large part of wall material, the thermo-sensitive release behavior was not so obvious. It is believed that the release of allopurinol from the microparticles is more dependent on the porous structure of microparticles than the conformational change of PNIPAM, created by the rapid evaporation of solvent during the spray dr...
Kim, Jong-Dukresearcher김종득researcher
한국과학기술원 : 생명화학공학과,
Issue Date
231078/325007  / 000995061

학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2003.8, [ xv, 126 p. ]


SPR (Surface Plasmon Resonance); Microparticles; Lectin; Bioadhesive; Oral Insulin Delivery; 경구 인슐린 전달; 표면 플라즈몬 공명; 마이크로입자; 렉틴; 생체접착성

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