Improving protein delivery from microparticles using blends of poly(DL lactide co-glycolide) and poly(ethylene oxide)-poly(propylene oxide) copolymers.
OBJECTIVE
Microparticles containing ovalbumin as a model for protein drugs were formulated from blends of poly(DL lactide-co-glycolide) and poly(ethylene oxide)-poly(propylene oxide) copolymers (Pluronic). The objectives were to achieve uniform release characteristics and improved protein delivery capacity.


METHODS
The water- in oil -in oil emulsion/solvent extraction technique was used for microparticle production.


RESULTS
A protein loading level of over 40% (w/w) was attained in microparticles having a mean diameter of approximately 5 microns. Linear protein release profiles over 25 days in vitro were exhibited by certain blend formulations incorporating hydrophilic Pluronic F127. The release profile tended to plateau after 10 days when the more hydrophobic Pluronic L121 copolymer was used to prepare microparticles. A delivery capacity of 3 micrograms OVA/mg particles/ day was achieved by formulation of microparticles using a 1:2 blend of PLG:Pluronic F127.


CONCLUSIONS
The w/o/o formulation approach in combination with PLG:Pluronic blends shows potential for improving the delivery of therapeutic proteins and peptides from microparticulate systems. Novel vaccine formulations are also feasible by incorporation of Pluronic L121 in the microparticles as a co-adjuvant.
Yeh
M K
MK
Department of Pharmaceutical Sciences, University of Nottingham, University Park, United Kingdom.
Davis
S S
SS
Coombes
A G
AG
D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D004655:Emulsions; D007700:Kinetics; D019344:Lactic Acid; D010047:Ovalbumin / Q000008:administration & dosage; D010316:Particle Size; D010592:Pharmaceutic Aids / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012996:Solutions
D004655:Emulsions; D010592:Pharmaceutic Aids; D011108:Polymers; D011409:Propylene Glycols; D011506:Proteins; D012996:Solutions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C012504:polypropylene glycol; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D010047:Ovalbumin