2003 Fiscal Year Final Research Report Summary
Development of Microencapsulated Peptide Drugs with Specific Controlled Release Functions by Air Suspension Coating Process
| Project/Area Number |
12672098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
ICHIKAWA Hideki Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (00248105)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMORI Yoshinobu Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60102927)
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| Project Period (FY) |
2000 – 2003
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| Keywords | Microcapsule / Controlled release / Peptide drug / Hydrogel / Coating / Polymer / Nanoparticle / Stimuli-sensitive polymer |
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| Research Abstract |
The aim of the present research project is to develop microcapsules with specific controlled release functions for peptide drug delivery. Three types of microcapsules with different drug-release mode were newly designed and their preparation was accomplished by the air suspension coating process. The proposed systems are directed to long-term delayed release for peroral colon-specific peptide delivery, periodically pulsatile release for chronophermacological peptide delivery and thermo-sensitive release for externally temperature-activated peptide delivery. The results obtained through this research project are summarized asfollows :
1.The microcapsules composed of a lactose core, a drug-layer and a coat of newly synthesized acrylic terpolymer made it possible to achieve a pH-independent delayed-release even for a macromolecular water-soluble substance with MW of 20,000. The microencapsulated insulin with this formulation was found to be released in a same manner and stable even after t
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he storage at 4℃ for 12 months. In vivo oral administration studies of the microcapsules revealed a relatively good correlation between in vitro drug-release profiles and in vivo drug-absorption behaviors.
2.Novel nano-sized components, i.e. poly(N-isbpropylacrylamide) with grafted poly(ethylene glycol)(p(NIPAAm-g-EG)) nanoparticles and biodegradable poly(e-caprolactone)(PCL), were prepared to fabricate the periodically pulsatile release microcapsules. The p(NIPAAm-g-EG) nanospheres had an ability to protect the incorporated insulin from high temperature and high shear stress that made the system a good candidate as a carrier for insulin for air suspension coating technology. The PCL nanoparticles showing a good film-formability could be prepared by a solvent-evaporation method, though further formulation studies are yet needed to reduce the water-permeability.
3.The microcapsules having an ability to thermosensitively control drug-release could be achieved by fabricating an ethylcellulose matrix coat containing nano-sized p(NIPAAm) hydrogels onto a drug-layered core. The microcapsules demonstrated a positively thermosensitive drug-release as expected. The present microcapsule membrane made it possible to obtain an 'on-off' pulsatile release, which could alter the release rate in the order of a minute, in response to stepwise temperature changes between 37 and 42℃. Less
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