Effect of cyclodextrins on α-chymotrypsin stability and loading in PLGA microspheres upon S/O/W encapsulation

✍ Scribed by Ingrid J. Castellanos; Giselle Flores; Kai Griebenow

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 309 KB
• Volume: 95
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20512

✦ Synopsis

The potential of cyclodextrins to stabilize a-chymotrypsin upon encapsulation in Poly(lactic-co-glycolic) acid (PLGA) microspheres using a solid-in-oil-in-water (s/o/w) technique was investigated. Two cyclodextrins, hydroxyl-propyl-b-cyclodextrin (HPbCD) and methyl-b-cyclodextrin (MbCD), one insoluble and the other soluble in methylene chloride, were used. The results demonstrate that HPbCD failed to stabilize achymotrypsin upon encapsulation. Specifically, 19% of the protein was aggregated and the specific activity of the enzyme was reduced to ca. 50% of that prior to encapsulation. In contrast, MbCD significantly decreased the formation of aggregates to 3% and the retained specific activity of the enzyme was approximately 90%. The co-lyophilization of a-chymotrypsin with MbCD prior to encapsulation was a requisite to preserve the protein stability in microspheres. Furthermore, MbCD prevented the loss of protein during the preparation of microspheres and the encapsulation efficiency was improved to 90%. Release experiments showed the use of MbCD modified the release profile: the burst release decreased from 54% (in the absence of the excipient) to 36%. The results suggest that MbCD might be a suitable excipient to improve protein stability in s/o/w encapsulation procedures.