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
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea; Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea; Department of Pharmacy, University of Lahore, Lahore, Pakistan.
Int J Pharm. 2017 Jun 15;525(1):92-100. doi: 10.1016/j.ijpharm.2017.04.032. Epub 2017 Apr 18.
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.
本研究旨在探讨甲氨蝶呤包封的超柔性脂质体凝胶（MTX - UDLs - gel）在佐剂诱导的关节炎大鼠模型中的体内抗风湿活性。将具有最佳磷脂酰胆碱与吐温80比例（7:3，w/w）的甲氨蝶呤包封超柔性脂质体（MTX - UDLs）掺入1%卡波姆凝胶中。对MTX - UDLs - gel的外观、澄清度、均匀性、pH值和药物含量进行了表征。使用Franz扩散池研究了MTX - UDLs - gel对大鼠皮肤的渗透情况。在完全弗氏佐剂（CFA）诱导的关节炎大鼠模型中，从水肿体积、爪部水肿和白细胞浸润评分、组织病理学分析以及炎性细胞因子水平方面评估了MTX - UDLs - gel的体内抗风湿活性。MTX - UDLs - gel表现出良好的均匀性和澄清度，pH值呈中性，药物含量约为99.5%。MTX从MTX - UDLs - gel中24小时的累积渗透量（164.6μg）分别比MTX - CLs - gel（113.3μg）和MTX - 普通凝胶（76.6μg）高1.5倍和2.15倍。在CFA诱导的关节炎大鼠模型中，MTX - UDLs - gel通过减少水肿体积、组织学评分和中性粒细胞积聚以及改善组织结构，显著减轻了炎症的严重程度。MTX - UDLs - gel有效抑制了爪部组织中促炎细胞因子TNF -α和IL -1β的表达。总之，所开发的MTX - UDLs - gel在将MTX有效递送至类风湿性关节炎的炎症关节方面具有巨大潜力。
