Effect of cyclodextrins on alpha-chymotrypsin stability and loading in PLGA microspheres upon S/O/W encapsulation.
The potential of cyclodextrins to stabilize alpha-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-beta-cyclodextrin (HPbetaCD) and methyl-beta-cyclodextrin (MbetaCD), one insoluble and the other soluble in methylene chloride, were used. The results demonstrate that HPbetaCD failed to stabilize alpha-chymotrypsin 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, MbetaCD significantly decreased the formation of aggregates to 3% and the retained specific activity of the enzyme was approximately 90%. The co-lyophilization of alpha-chymotrypsin with MbetaCD prior to encapsulation was a requisite to preserve the protein stability in microspheres. Furthermore, MbetaCD prevented the loss of protein during the preparation of microspheres and the encapsulation efficiency was improved to 90%. Release experiments showed the use of MbetaCD modified the release profile: the burst release decreased from 54% (in the absence of the excipient) to 36%. The results suggest that MbetaCD might be a suitable excipient to improve protein stability in s/o/w encapsulation procedures.
Department of Chemistry, University of Puerto Rico, Río Piedras Campus, P.O. Box 23346, San Juan, Puerto Rico 00931-3346.
Ingrid J
IJ
Castellanos
Giselle
G
Flores
Kai
K
Griebenow
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002918:Chymotrypsin / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004655:Emulsions; D004795:Enzyme Stability / Q000187:drug effects; D005079:Excipients / Q000737:chemistry* / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D008752:Methylene Chloride / Q000737:chemistry; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004655:Emulsions; D005079:Excipients; D011108:Polymers; D012997:Solvents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008752:Methylene Chloride; D002918:Chymotrypsin; C117608:alpha-chymotrypsin