The effect of gamma-irradiation on PLGA/PEG microspheres containing ovalbumin.
Poly(ethylene glycol) (PEG) and sodium chloride (NaCl) are excipients used in PLGA microsphere preparation to stabilize proteins and reduce their burst release. No information is till now available in the literature on the effect due to the use of such excipients on the biopharmaceutical performance of gamma-irradiated microparticulate systems. On this purpose, different batches of microspheres containing ovalbumin (OVA) were prepared by using a PLGA 50:50 (average Mr: 13000), different amounts of PEG (Mr: 400 or 4000) and/or sodium chloride. The non-irradiated and irradiated microspheres were characterized in terms of morphology (SEM, particle size distribution), OVA and PEG content and in vitro OVA release. Radiolysis mechanisms of OVA and OVA loaded microspheres were investigated by EPR analysis. Gamma irradiation affects either microsphere morphology or the release of OVA as a function of the amount of PEG, and the use of NaCl. Irradiation significantly reduces release rate of protein from the microspheres containing 15% and 30% of PEG and from controls (microspheres without additives), while no significative effect on protein release rate is highlighted on microspheres containing lower amounts of PEG. EPR investigation shows that increasing amounts of PEG up to 30% have a perturbation effect on OVA radiolysis path.
Dorati
Rossella
R
Department of Pharmaceutical Chemistry, University of Pavia, V.le Taramelli 12, 27100 Pavia, Italy.
Genta
Ida
I
Montanari
Luisa
L
Cilurzo
Francesco
F
Buttafava
Armando
A
Faucitano
Antonio
A
Conti
Bice
B
D005079:Excipients / Q000737:chemistry; D005720:Gamma Rays; D019344:Lactic Acid / Q000737:chemistry* / Q000528:radiation effects*; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010047:Ovalbumin / Q000737:chemistry* / Q000528:radiation effects* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000528:radiation effects*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000528:radiation effects*; D011506:Proteins / Q000032:analysis; D012965:Sodium Chloride / Q000737:chemistry
D005079:Excipients; D011108:Polymers; D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D010047:Ovalbumin