Effects of additives and processing parameters on the initial burst release of protein from poly(lactic-co-glycolic acid) microspheres.
The aim of this study is to investigate both the effects of hydrophilic additives and combined processing parameters on the in vitro release of a model protein, bovine serum albumin (BSA), from poly(lactic-co-glycolic acid) (PLGA) microspheres. Additives including beta-cyclodextrin, HP-beta-cyclodextrin, poly(ethylene glycol) (PEG) 6000, and sorbitol, and processing parameters such as the poly(vinyl alcohol) (PVA) concentration, emulsification temperature, aqueous/oil phase, evaporation method, and dehydration method were evaluated. PLGA microspheres were all prepared by the double-emulsion solvent extraction/evaporation method, and the results showed that no statistically significant differences of particle sizes and entrapment efficiencies appeared. Interestingly, the initial burst releases were markedly changed by both additives and processing parameters. Initial burst releases were accelerated by hydrophilic additives except for PEG 6000 and were retarded by the formulation composed of higher PVA concentration, tween-20 as an emulsifier in the internal aqueous phase, glycerol in the oil phase, and inorganic salt in the external aqueous phase, and operated at low temperature. Scanning electron microscopy showed that the more porous and dimpled the structure on the surface of the PLGA microspheres, the larger the initial burst release. The microspheres that displayed a relatively smooth and compact surface showed the least burst release.
Zheng
Cai-Hong
CH
Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University; Hangzhou 310031, China.
Gao
Jian-Qing
JQ
Liang
Wen-Quan
WQ
Yu
He-Yong
HY
Zhang
Yi-Li
YL
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry*; D006016:Glycolates / Q000737:chemistry*; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000737:chemistry
D004337:Drug Carriers; D005079:Excipients; D006016:Glycolates; D011506:Proteins; D047392:beta-Cyclodextrins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D011092:Polyethylene Glycols; D013012:Sorbitol