title: Methylprednisolone-loaded PLGA microspheres: a new formulation for sustained release via intra-articular administration. A comparison study with methylprednisolone acetate in rats.
abstract: Methylprednisolone (MP) released by poly(d,l-lactide-co-glycolide) microspheres (PLGA MS) was monitored in plasma after intra-articular (i.a.) administration into rat joint. A validated LC-ESI-MS/MS method was used to quantify the plasmatic concentrations of MP. The calculated pharmacokinetic parameters were compared to those obtained after the i.a. administration of a commercially available suspension of MP acetate (MPA). Different pharmacokinetic profiles were observed in the two formulations, and a lower peak level (C(max) = 13.7 ± 4.3 ng · mL(-1)) and AUC(0-72 h) (198 ± 45 ng · mL(-1) · h) were observed for MP-PLGA MS than MPA (C(max) = 18.4 ± 2.7 ng · mL(-1)) and AUC(0-72 h) (943 ± 249 ng · mL(-1) · h). The administration of MP-PLGA MS resulted in a rapid increase in the MP concentration at 30 min, with a t(max) at 0.8 ± 0.3 h. Instead, for the MPA suspension the t(max) was 32.0 ± 13.9 h. These differences were indirectly confirmed by the evaluation of the extra-articular effects, namely, carrageenan-induced paw edema, since MP-PLGA MS showed a lower anti-inflammatory activity than MPA.
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. alessia.panusa@iss.it
authors.forename: Alessia
authors.initials: A
authors.lastname: Panusa
authors.forename: Francesca
authors.initials: F
authors.lastname: Selmin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossoni
authors.forename: Marina
authors.initials: M
authors.lastname: Carini
authors.forename: Francesco
authors.initials: F
authors.lastname: Cilurzo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Aldini
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002853:Chromatography, Liquid; D003692:Delayed-Action Preparations; D007596:Joints; D019344:Lactic Acid / Q000737:chemistry*; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008775:Methylprednisolone