Enhanced anti-rheumatic activity of methotrexate-entrapped ultradeformable liposomal gel in adjuvant-induced arthritis rat model

[Display omitted] 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 t...

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Bibliographic Details
Published in:International journal of pharmaceutics 2017-06, Vol.525 (1), p.92-100
Main Authors: Zeb, Alam, Qureshi, Omer Salman, Yu, Chan-Hee, Akram, Muhammad, Kim, Hyung-Seo, Kim, Myung-Sic, Kang, Jong-Ho, Majid, Arshad, Chang, Sun-Young, Bae, Ok-Nam, Kim, Jin-Ki
Format: Article
Language:English
Subjects:
Animals
Arthritis, Experimental - drug therapy
Arthritis, Rheumatoid
Complete Freund’s adjuvant
Inflammation
Interleukin-1beta - metabolism
Liposomes - chemistry
Methotrexate
Methotrexate - administration & dosage
Methotrexate - pharmacology
Rats
Rheumatoid arthritis
Transdermal delivery
Tumor Necrosis Factor-alpha - metabolism
Ultradeformable liposomes
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Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.04.032