title: PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies.
abstract: The aim of this study was an in vitro/in vivo investigation on poly(lactide-co-glycolide) (PLGA) microspheres as carriers for the topical ocular delivery of a peptide drug vancomycin (VA). The microspheres were prepared by an emulsification/spray-drying technique that can be proposed as an alternative to the double emulsion method for preparation of peptide-loaded microparticles. The drug encapsulation efficiencies were close to the theoretical values (84.2-99.5%); the average particle size, expressed as dvs, was about 11 microm. The microspheres were able to modulate the in vitro drug release of VA with a behavior dependent on their composition: the highest drug content corresponded to the highest release rate. In vivo studies were carried out by assessing the pharmacokinetic profile of VA in the aqueous humor of rabbits after topical administration of aqueous suspensions of microspheres. High and prolonged VA concentrations and increased AUC values (2-fold) with respect to an aqueous solution of the drug were observed. Increasing the viscosity of the microsphere suspension by addition of a suspending-viscosizing agent (hydroxypropylcellulose) did not produce an increase of the ocular bioavailability. PLGA microspheres can be proposed as a system for ocular delivery of peptide drugs.
authors.affiliation: Dipartimento di Scienze del Farmaco, University of Sassari, Sassari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chetoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Cossu
authors.forename: Maria Gemma
authors.initials: MG
authors.lastname: Alvarez
authors.forename: Marco Fabrizio
authors.initials: MF
authors.lastname: Saettone
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008863:Microspheres; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D045703:Emulsifying Agents; D010455:Peptides; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014640:Vancomycin