Alpha-methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy.

Abstract

A glycinate derivative of alpha-methylprednisolone (MP) was prepared and conjugated to a linear cyclodextrin polymer (CDP) with a loading of 12.4% w/w. The polymer conjugate (CDP-MP) self-assembled into nanoparticles with a size of 27 nm. Release kinetics of MP from the polymer conjugate showed a half-life (t1/2) of 50 h in phosphate buffer solution (PBS) and 19 h in human plasma. In vitro, the proliferation of human lymphocytes was suppressed to a similar extent but with a delayed effect when CDP-MP was compared with free MP. In vivo, CDP-MP was administered intravenously to mice with collagen-induced arthritis and compared with free MP. CDP-MP was administered weekly for six weeks (0.07, 0.7, and 7 mg/kg/week) and MP was administered daily for six weeks (0.01, 0.1, and 1 mg/kg/day). Body weight changes were minimal in all animals. After 28 days, a significant decrease in arthritis score was observed in animals treated weekly with an intermediate or high dose of CDP-MP. Additionally, dorsoplantar swelling was reduced to baseline in animals treated with CDP-MP at the intermediate and high dose level. Histological evaluation showed a reduction in synovitis, pannus formation and disruption of architecture at the highest dose level of CDP-MP. MP administered daily at equivalent cumulative doses showed minimal efficacy in this model. This study demonstrates that conjugation of MP to a cyclodextrin-polymer may improve its efficacy, leading to lower doses and less frequent administration for a safer and more convenient management of rheumatoid arthritis.

• Authors: Jungyeon Hwang, Kathleen Rodgers, James C Oliver, Thomas Schluep
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 3 Issue 3 Pg. 359-71 ( 2008) ISSN: 1176-9114 [Print] New Zealand
• PMID: 18990945 (Publication Type: Journal Article)

Chemical References

• Cyclodextrins
• Drug Carriers
• Polymers
• Methylprednisolone

Topics

• Animals
• Arthritis, Rheumatoid (drug therapy, pathology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cyclodextrins (administration & dosage, chemistry)
• Drug Carriers (chemistry)
• Humans
• Lymphocytes (cytology, drug effects)
• Methylprednisolone (administration & dosage, chemistry)
• Mice
• Nanoparticles (chemistry, ultrastructure)
• Polymers (chemistry)
• Treatment Outcome