Investigation of the factors influencing the release rates of cyclosporin A-loaded micro- and nanoparticles prepared by high-pressure homogenizer.
An oil-in-water solvent evaporation method was used to prepare cyclosporin A (CyA)-loaded particles varying in size (nanoparticles, 'small-sized' microparticles, 'large-sized' microparticles), polymer compositions [poly(D,L-lactide-co-glycolic acid) (PLGA) 50/50, PLGA 85/15, poly(D,L-lactic acid) (PLA)] and additive fatty acid ester (ethyl myristate; EM). The particles were characterized for drug loading and entrapment efficiency by high-performance liquid chromatography, particle size by dynamic light scattering and surface morphology by scanning electron microscopy (SEM). In vitro release kinetics were studied using a modified dialysis method. The results showed drug loadings ranging from 6.48 to 9.01% with high encapsulation efficiency (71.2-98.9%). SEM studies showed discrete and spherical particles with smooth surfaces, whereas rather gross surface defects resulted from the incorporation of EM as an additive. The release profiles of various formulations approximated zero-order release kinetics in the first 3 weeks with a negligible initial burst. In general, the smaller the particle size and the higher the glycolic acid content in the copolymer, the faster the release of CyA. The effect of EM on the release profile appeared to be rather complex since an increased release rate was observed from EM containing PLGA 50/50 particles, whereas the incorporation of EM into the PLGA 85/15 and PLA particles led to a decreased release rate. Further investigation needs to be performed to elucidate the reason why EM influences the CyA release differently depending on the particle size and polymer type.
Lee
Woo-kyoung
WK
School of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, South Korea.
Park
Jong-yeun
JY
Yang
Eun Hee
EH
Suh
Hearan
H
Kim
Sung Hoon
SH
Chung
Doo Soo
DS
Choi
Kihwan
K
Yang
Chul Woo
CW
Park
Jong-sang
JS
D016572:Cyclosporine / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009226:Myristates / Q000737:chemistry; D036103:Nanotechnology; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011312:Pressure; D012995:Solubility; D013997:Time Factors
D009226:Myristates; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C032396:ethyl myristate; D016572:Cyclosporine