&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy

Jungyeon Hwang1, Kathleen Rodgers2, James C Oliver3, Thomas Schluep11Insert Therapeutics, Inc., Pasadena, CA, USA; 2Livingston Research Institute, Los Angeles, CA, USA; James C Oliver, Peptagen, Inc., Raleigh, NC USAAbstract: A glycinate derivative of &alpha;-methylprednisolone (MP) was prep...

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Autores principales:	Jungyeon Hwang, Kathleen Rodgers, James C Oliver, Thomas Schluep
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/25cabd130b424973a99846497d2ca988
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spelling	oai:doaj.org-article:25cabd130b424973a99846497d2ca9882021-12-02T05:07:53Z&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy1176-91141178-2013https://doaj.org/article/25cabd130b424973a99846497d2ca9882008-10-01T00:00:00Zhttp://www.dovepress.com/alpha-methylprednisolone-conjugated-cyclodextrin-polymer-based-nanopar-a2436https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jungyeon Hwang1, Kathleen Rodgers2, James C Oliver3, Thomas Schluep11Insert Therapeutics, Inc., Pasadena, CA, USA; 2Livingston Research Institute, Los Angeles, CA, USA; James C Oliver, Peptagen, Inc., Raleigh, NC USAAbstract: 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.Keywords: &alpha;-methylprednisolone (MP), cyclodextrin polymer (CDP), polymer conjugate (CDP-MP), rheumatoid arthritis (RA), enhanced permeability and retention effect (EPR) Jungyeon HwangKathleen RodgersJames C OliverThomas SchluepDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2008, Iss Issue 3, Pp 359-371 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Jungyeon Hwang Kathleen Rodgers James C Oliver Thomas Schluep &alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
description	Jungyeon Hwang1, Kathleen Rodgers2, James C Oliver3, Thomas Schluep11Insert Therapeutics, Inc., Pasadena, CA, USA; 2Livingston Research Institute, Los Angeles, CA, USA; James C Oliver, Peptagen, Inc., Raleigh, NC USAAbstract: 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.Keywords: &alpha;-methylprednisolone (MP), cyclodextrin polymer (CDP), polymer conjugate (CDP-MP), rheumatoid arthritis (RA), enhanced permeability and retention effect (EPR)
format	article
author	Jungyeon Hwang Kathleen Rodgers James C Oliver Thomas Schluep
author_facet	Jungyeon Hwang Kathleen Rodgers James C Oliver Thomas Schluep
author_sort	Jungyeon Hwang
title	&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
title_short	&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
title_full	&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
title_fullStr	&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
title_full_unstemmed	&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
title_sort	&alpha;-methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/25cabd130b424973a99846497d2ca988
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&amp;alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy

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