期刊
JOURNAL OF CONTROLLED RELEASE
卷 70, 期 1-2, 页码 193-202出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(00)00352-7
关键词
biodegradable microspheres; insulin-like growth factor-I; poly(lactide-co-glycolide); protein stability
This study aimed at developing a controlled drug delivery system for recombinant human insulin-like growth factor-I (IGF-I) for localized delivery in bone healing. IGF-I was microencapsulated into an end-group uncapped 14 kDa poly( D.L-lactide-co-glycolide) 50:50 (PLGA 50:50) by solvent extraction from a W-1/O/W-2 dispersion. Prior to encapsulation, IGF-I was exposed to ultrasonication in a water/dichloromethane dispersion, and its stability tested in the presence acid absence of various excipients in the W-1 phase. HPLC and RIA were used for the assessment of IGF-I stability. Microencapsulated IGF-I was tested again for its structural intactness and also for in vitro release from various formulations containing appropriate co-encapsulated excipients. A specific fat cell assay was used to determine the biological activity of released IGF-I. Moderate ultrasonic treatment of aqueous IGF-I/dichloromethane mixtures caused approx. 50% IGF-I degradation. However, IGF-I was fully protected when bovine serum albumin, succinylated gelatin or poly(ethyleneglycol) were added to the aqueous IGF-I. Co-encapsulation of these excipients protected efficiently the protein upon microencapsulation. IGF-I release from microsphere formulations was sustained for up to 13 days featuring a moderately pulsatile pattern, depending on the microsphere composition. Typically, the amounts of IGF-I released within the first 14 b (burst) and during the second release pulse were in the order of 20 and 40%, respectively, of the total dose. The biological activity of released IGF-I was confirmed at selected time-points by the fat cell assay. In conclusion. the developed microspheres proved to be suitable to release biologically intact IGF-I over up to 13 days, a time-period considered to be relevant to promote bone fracture healing. (C) 2001 Elsevier Science B.V. All rights reserved.
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