Bh. Woo et al., Preparation and characterization of a composite PLGA and poly(acryloyl hydroxyethyl starch) microsphere system for protein delivery, PHARM RES, 18(11), 2001, pp. 1600-1606
Purpose. To prepare and characterize a novel composite microsphere system b
ased on poly (D,L-lactide-co-glycolide) (PLGA) and poly(acryloyl hydroxyeth
yl starch) (acHES) hydrogel for controlled protein delivery.
Methods. Model proteins, bovine serum albumin, and horseradish peroxidase w
ere encapsulated in the acHES hydrogel, and then the protein-containing acH
ES hydrogel particles were fabricated in the PLGA matrix by a solvent extra
ction or evaporation method. The protein-loaded PLGA-acHES composite micros
pheres were characterized for protein loading efficiency, particle size, an
d in vitro protein release. Protein stability was examined by size-exclusio
n chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis
(SDS-PAGE), and monitoring the enzymatic activity.
Results. Scanning electron microscopy showed discrete PLGA microspheres con
taining many acHES particles. The composite microspheres were spherical and
smooth in size range of 39-93 mum. The drug loading efficiency ranged from
51 to 101%. The composite Microspheres showed more favorable in vitro rele
ase than conventional PLGA microspheres. The composite microspheres showed
20% less initial with a gradual sustained release compared to high burst (s
imilar to 60 %) followed by a very slow release with the conventional PLGA
microspheres. The composite microspheres also stabilized encapsulated prote
ins from the loss of activity during the microsphere preparation and releas
e. Proteins extracted from the composite microspheres showed good stability
without protein degradation products and structural integrity chances in t
he size-exclusion chromatography and SDS-PAGE analyses. Horseradish peroxid
ase extracted from microspheres retained more than 81% enzymatic activity.
Conclusion. The PLGA-acHES composite microsphere system could be useful for
the controlled delivery of protein drugs.