Preparation and characterization of protein loaded microspheres based on a hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid).
The purpose of this study was to investigate the suitability of a novel hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA), as controlled release system for pharmaceutical proteins. Dextran Blue (as a macromolecular model compound) and lysozyme-loaded PLHMGA and PLGA (control formulation) microspheres were prepared by a solvent evaporation technique. The Dextran Blue and lysozyme loaded PLHMGA microspheres prepared with 10% polymer solution showed, because of a high porosity, a high burst release (35-75%) and the remaining content was released in a sustained manner for 15-20 days. The microspheres prepared with 15 and 20% polymer solution had a lower porosity and showed a pulsed release after day 8 and in 27 days they released more than 90% of Blue Dextran. The release of lysozyme was incomplete, likely due to aggregation of part of the encapsulated protein. Spectroscopic analysis of the released lysozyme indicated fully preserved secondary/tertiary structure and an enzyme activity assay showed that the specific activity of the released protein was maintained. An in vitro degradation study showed that the release of Blue Dextran and lysozyme is essentially controlled by the degradation of the microspheres. This study shows that microspheres made of the hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid), are promising systems for the controlled release of pharmaceutical proteins.
Ghassemi
A H
AH
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
van Steenbergen
M J
MJ
Talsma
H
H
van Nostrum
C F
CF
Jiskoot
W
W
Crommelin
D J A
DJ
Hennink
W E
WE
D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008837:Micrococcus / Q000378:metabolism; D008863:Microspheres; D009113:Muramidase / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011487:Protein Conformation; D013499:Surface Properties
D003692:Delayed-Action Preparations; D003911:Dextrans; D011091:Polyesters; C544675:poly(lactic-co-hydroxymethyl glycolic acid); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C017080:blue dextran; D009113:Muramidase