Prednisolone-loaded PLGA microspheres. in vitro characterization and in vivo application in adjuvant-induced arthritis in mice

AAPS PharmSciTech. 2010 Jun;11(2):859-69. doi: 10.1208/s12249-010-9445-5. Epub 2010 May 19.

Abstract

This study aimed at preparation of a sustained-release steroidal treatment for chronic inflammatory conditions, such as rheumatoid arthritis. To achieve such a goal, biodegradable poly-lactide-co-glycolide prednisolone-loaded microspheres were prepared using o/w emulsion solvent evaporation method. Formulation parameters were adjusted so as to optimize the microsphere characteristics. The prepared microspheres exhibited smooth and intact surfaces, with average size range not exceeding 65 microm. The encapsulation efficiency percent of most microsphere formulations fell within the range of 25-68%. Drug release from these microspheres took place over 4 weeks, with near-to-zero-order patterns. Two successful formulations were chosen for the treatment of unilateral arthritis, induced in mice using Freund's complete adjuvant (FCA). Inflammatory signs of adjuvant arthritis included severe swelling of the FCA-injected limbs, in addition to many histopathological lesions. These included inflammatory cell infiltration, synovial hyperplasia, cartilage, and bone erosion. Parenteral administration of the selected formulae dramatically reduced the swelling of the FCA-injected limbs. In addition, histological examination revealed that the microsphere treatment protocol efficiently protected cartilages and bones of mice, injected with FCA initial and booster doses, from erosion. These results could not be achieved by a single prednisolone dose of 5 mg/kg.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Arthritis / chemically induced
  • Arthritis / diagnosis
  • Arthritis / drug therapy*
  • Capsules*
  • Diffusion
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemical synthesis*
  • Drug Compounding / methods
  • Female
  • Freund's Adjuvant
  • Lactic Acid / chemistry*
  • Mice
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Prednisolone / administration & dosage*
  • Prednisolone / chemistry*
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Capsules
  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Freund's Adjuvant
  • Prednisolone