Drug Delivery Laboratory, TIFAC Center of Relevance and Excellence in NDDS, Department of Pharmacy, The M.S. University of Baroda, Vadodara, India.
J Liposome Res. 2011 Jun;21(2):134-40. doi: 10.3109/08982104.2010.492476. Epub 2010 Jun 18.
Methotrexate (MTX) is indicated in the symptomatic control of severe, recalcitrant, and disabling psoriasis. The oral or parenteral route of administration causes systemic toxicity. The topical route of delivery, though, reduces systemic toxicity and has limited applicability due to restricted permeability. Liposomal and niosomal MTX topical formulations have also been investigated with limited success to achieve drug localization in the skin. Menthol has been suggested in conditions of psoriasis, in addition to its skin-penetration-enhancing effect on drugs. The present work aimed at investigating the potential benefits of combining menthol with MTX in a vesicular gel base for not only improving the penetration and dermal availability of MTX, but also to render such a formulation more effective with greater patient acceptability. MTX liposomes were prepared by thin-film hydration, and the vesicles were characterized for drug-entrapment efficiency, size, and morphology. These liposomal vesicles were incorporated in a gel base, and this vesicular gel was evaluated for transdermal drug permeation and extent of drug accumulation in the skin, using a rat skin ex vivo model. Skin histology studies were carried out to investigate any structural changes caused by the permeation enhancers. Antipsoriatic efficacy of the formulations was tested in vivo, using the rat tail model. The results indicated that the vesicular gel containing menthol could cause maximum drug retention in the skin. The skin treated with menthol had a disrupted epidermis and microcavities. The in vivo studies also ascertained the effectiveness of the formulation in inducing a normal pattern of differentiation in the rat tail skin that initially showed parakeratosis, which is also characteristic of psoriatic epidermis. These results show the potential of vesicular gel containing MTX and menthol to improve penetration into the skin and cause drug retention in skin appendages.
甲氨蝶呤（MTX）适用于严重、难治性和致残性银屑病的症状控制。口服或肠胃外给药途径会导致全身毒性。然而，局部给药途径可降低全身毒性，但由于渗透性有限，其适用性有限。已经研究了脂质体和非离子体 MTX 局部制剂，以实现药物在皮肤中的定位，但收效有限。薄荷醇除了具有增强药物透皮作用外，还在银屑病等疾病中得到了应用。本研究旨在探讨将薄荷醇与 MTX 联合应用于囊泡凝胶基质的潜在益处，不仅可以提高 MTX 的渗透和皮肤可达性，而且可以提高制剂的有效性，提高患者的接受度。采用薄膜水化法制备 MTX 脂质体，并对其包封效率、粒径和形态进行了表征。将这些脂质体囊泡掺入凝胶基质中，采用大鼠皮肤离体模型评价其透皮药物渗透和皮肤药物蓄积程度。进行皮肤组织学研究，以研究渗透增强剂引起的任何结构变化。采用大鼠尾巴模型进行体内抗银屑病疗效研究。结果表明，含有薄荷醇的囊泡凝胶可以使药物在皮肤中最大程度地保留。用薄荷醇处理的皮肤表皮破裂，出现微小空洞。体内研究还证实了该制剂在诱导大鼠尾巴皮肤正常分化模式方面的有效性，该制剂最初表现出角化不全，这也是银屑病表皮的特征。这些结果表明，含有 MTX 和薄荷醇的囊泡凝胶具有改善药物渗透和在皮肤附属器中保留药物的潜力。
