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

被引：65
作者：
Zeb, Alam [1 ,2 ]
Qureshi, Omer Salman [1 ,3 ]
Yu, Chan-Hee [1 ]
Akram, Muhammad [4 ]
Kim, Hyung-Seo [1 ]
Kim, Myung-Sic [1 ]
Kang, Jong -Ho [1 ]
Majid, Arshad [5 ]
Chang, Sun-Young [6 ]
Bae, Ok-Nam [1 ]
Kim, Jin-Ki [1 ]
机构：
[1] Hanyang Univ, Inst Pharmaceut Sci & Technol, Coll Pharm, 55 Hanyangdaehak Ro, Ansan 15588, Gyeonggi, South Korea
[2] Riphah Int Univ, Riphah Inst Pharmaceut Sci, Islamabad, Pakistan
[3] Univ Lahore, Dept Pharm, Lahore, Pakistan
[4] Univ Sindh, Fac Pharm, Jamshoro, Pakistan
[5] Univ Sheffield, Sheffield Inst Translat Neurosci, Sheffield, S Yorkshire, England
[6] Ajou Univ, Coll Pharm, Suwon, Gyeonggi, South Korea
来源：
INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2017年 / 525卷 / 01期
关键词：
Methotrexate; Ultradeformable liposomes; Rheumatoid arthritis; Transdermal delivery; Complete Freund's adjuvant; Inflammation; SOLID LIPID NANOPARTICLES; FOLATE-TARGETED NANOPARTICLES; RHEUMATOID-ARTHRITIS; IN-VIVO; TRANSDERMAL DELIVERY; SKIN DELIVERY; INFLAMMATORY CYTOKINE; POTENTIAL TREATMENT; TOPICAL DELIVERY; DRUG CARRIERS;
D O I：
10.1016/j.ijpharm.2017.04.032
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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 24 h from MTX-UDLs-gel (164.6 mu g) was 1.5 and 2.15 times higher than that of MTX-CLs-gel (113.3 mu g) and MTX-plain-gel (76.6 mu g), 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. MTXUDLs- gel effectively suppressed the expression of pro-inflammatory cytokines, TNF-alpha and IL-beta, 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. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码：92 / 100
页数：9
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