Efficacy study of vesicular gel containing methotrexate and menthol combination on parakeratotic rat skin model.
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.
Nagle
Amrita
A
Drug Delivery Laboratory, TIFAC Center of Relevance and Excellence in NDDS, Department of Pharmacy, The M.S. University of Baroda, Vadodara, India.
Goyal
Amit K
AK
Kesarla
Rajesh
R
Murthy
Rayasa R
RR
D000287:Administration, Topical; D000818:Animals; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D005779:Immunodiffusion; D008081:Liposomes / Q000008:administration & dosage / Q000138:chemical synthesis; D008297:Male; D008610:Menthol / Q000008:administration & dosage* / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D010241:Parakeratosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012869:Skin Absorption / Q000187:drug effects*; D046509:Tissue Culture Techniques
D003879:Dermatologic Agents; D004338:Drug Combinations; D005782:Gels; D008081:Liposomes; D008610:Menthol; D008727:Methotrexate