Computer modeling assisted design of monodisperse PLGA microspheres with controlled porosity affords zero order release of an encapsulated macromolecule for 3 months.
OBJECTIVE
The aim of this study was the development of poly(D,L-lactide-co-glycolide) (PLGA) microspheres with controlled porosity, to obtain microspheres that afford continuous release of a macromolecular model compound (blue dextran).


METHODS
PLGA microspheres with a size of around 40 μm and narrow size distribution (span value of 0.3) were prepared with a double emulsion membrane emulsification method. Gene expression programming (GEP) analysis was applied to design and formulate a batch of microspheres with controlled porosity that shows continuous release of blue dextran.


RESULTS
Low porous microspheres with a high loading efficiency were formed at high polymer concentrations (30% w/w in the oil phase) and were characterized with a burst release <10% and a three-phasic release profile of blue dextran. Increasing porosity (10% w/w polymer concentrations), a sustained release of blue dextran was obtained albeit with up to 40% of burst release. The desired formulation, calculated by GEP, resulted in microspheres with 72% loading efficiency and intermediate porosity. Blue dextran was indeed released continuously in almost a zero order manner over a period of 3 months after an initial small burst release of 9%.


CONCLUSIONS
By fine-tuning the porosity, the release profile of PLGA microspheres for macromolecules can be predicted and changed from a three-phasic to a continuous release.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Filis
F
Kazazi-Hyseni
Mariana
M
Landin
Audrey
A
Lathuile
Gert J
GJ
Veldhuis
Sima
S
Rahimian
Wim E
WE
Hennink
Robbert Jan
RJ
Kok
Cornelus F
CF
van Nostrum
D003198:Computer Simulation; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D015195:Drug Design; D065546:Drug Liberation; D004867:Equipment Design; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D013499:Surface Properties; D013997:Time Factors
D003911:Dextrans; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C017080:blue dextran