Study of gamma-irradiation effects on aciclovir poly(D,L-lactic-co-glycolic) acid microspheres for intravitreal administration.
Gamma-irradiation effects on aciclovir poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres, with gelatin as additive, were studied. Microspheres with a 2:2:10 aciclovir:gelatin:polymer ratio were prepared by the solvent evaporation method and sterilised by gamma-irradiation at a dose of 25 kGy. Loading efficiency, morphology (particle size analysis, scanning electron microscopy (SEM)), physical chemistry (infrared (IR) absorption spectrophotometry, differential scanning calorimetry (DSC), X-ray diffraction and gel permeation chromatography (GPC)) and in vitro release assays for 73 days were performed to evaluate the sterilisation effect on microsphere characteristics. After gamma-irradiation, no surface changes were observed by SEM. Microparticle mean diameter and aciclovir loading efficiency were not affected by gamma-ray exposition. IR spectroscopy, DSC and X-ray diffraction showed no modification of the bulk properties of the microspheres or their components. The controlled release profiles of aciclovir-loaded microspheres for 73 days were not altered upon exposure to gamma-irradiation. GPC measurements showed a decrease in molecular weight of the polymer. The sterilisation method is adequate because microspheres underwent no change after exposition to gamma-irradiation. These favourable properties of the aciclovir-loaded microspheres make them a suitable system for the intravitreal treatment of herpes virus infections, in an animal model.
Martínez-Sancho
Concepción
C
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Plaza Ramon y Cajal sn, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Herrero-Vanrell
Rocío
R
Negro
Sofía
S
D000212:Acyclovir / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects*; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D004333:Drug Administration Routes; D005720:Gamma Rays; D019344:Lactic Acid / Q000737:chemistry / Q000528:radiation effects*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry / Q000528:radiation effects*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000528:radiation effects*; D013055:Spectrophotometry, Infrared; D013242:Sterilization / Q000379:methods; D014961:X-Ray Diffraction
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000212:Acyclovir