期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 311, 期 1-2, 页码 187-195出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2005.12.033
关键词
chitosan microspheres; uniform size; membrane emulsification; step-wise crosslinking; insulin
Chitosan microsphere has potential applications in orally and other mucosally administration of protein and peptide drug, because it shows excellent mucoadhesive and permeation enhancing effect across the biological surfaces. The control of the size and size distribution of chitosan microsphere is necessary in order to improve its reproducibility, bioavailability and repeatable release behavior. Furthermore, it is a big challenge how to maintain the chemical stability of protein drug and improve its release behavior in the preparation of chitosan microspheres, because conventional crosslinking method by glutaraldehyde cannot be used in encapsulation of protein drug containing amino group. In this study, we established method to prepare uniform-sized microsphere, and solve above problems by combining it special membrane emulsification technique and a step-wise crosslinking method. The preparative condition was optimized, and the chemical stability of protein, encapsulation efficiency, and release behavior were compared with conventional preparative method of drug-loaded chitosan microspheres. As a result, fairly uniform chitosan microspheres were obtained with a coefficient of variation (C.V.) value less than 11%, and the step-wise crosslinking method developed specially for membrane emulsification method provided the microspheres with higher encapsulation efficiency (80%), higher chemical stability of insulin (> 95%), lower burst release and steady release behavior. (c) 2005 Elsevier B.V. All rights reserved.
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