Zeb, A., Qureshi, O.S., Yu, C.-H. et al. (8 more authors) (2017) Enhanced anti-rheumatic activity of methotrexate-entrapped ultradeformable liposomal gel in adjuvant-induced arthritis rat model. International Journal of Pharmaceutics, 525 (1). pp. 92-100. ISSN 0378-5173
Abstract
The aim of this study is to investigate in vivo anti-rheumatic activity of methotrexate-entrapped ultradeformable liposomal gel (MTX-UDLs-gel) in adjuvant-induced arthritis rat model. Methotrexate-entrapped ultradeformable liposomes (MTX-UDLs) with the optimal phosphatidylcholine to Tween 80 ratio (7:3, w/w) were incorporated into 1% Carbopol gel. MTX-UDLs-gel was characterized in terms of appearance, clarity, homogeneity, pH and drug content. The permeation of MTX-UDLs-gel across rat skin was investigated using Franz diffusion cell. In vivo anti-rheumatic activity of MTX-UDLs-gel was assessed in terms of edema volume, paw edema and leukocyte infiltration scores, histopathological analysis and inflammatory cytokines level in complete Freund's adjuvant (CFA)-induced arthritis rat model. MTX-UDLs-gel showed good homogeneity and clarity, neutral pH and about 99.5% drug content. The cumulative amount of MTX permeated for 24h from MTX-UDLs-gel (164.6μg) was 1.5 and 2.15 times higher than that of MTX-CLs-gel (113.3μg) and MTX-plain-gel (76.6μg), respectively. MTX-UDLs-gel significantly alleviated the severity of inflammation by reducing edema volume, histological scores and accumulation of neutrophils and improving tissue architecture in CFA-induced arthritis rat model. MTX-UDLs-gel effectively suppressed the expression of pro-inflammatory cytokines, TNF-α and IL-1β, in paw tissues. In conclusion, the developed MTX-UDLs-gel has a great potential for effective delivery of MTX into the inflamed joints in rheumatoid arthritis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier. |
Keywords: | Complete Freund’s adjuvant; Inflammation; Methotrexate; Rheumatoid arthritis; Transdermal delivery; Ultradeformable liposomes |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number NEUROCARE UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 02 May 2017 14:26 |
Last Modified: | 02 May 2017 14:26 |
Published Version: | https://doi.org/10.1016/j.ijpharm.2017.04.032 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.ijpharm.2017.04.032 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115870 |