title: Ethogel topical formulation for increasing the local bioavailability of 5-fluorouracil:  a mechanistic study.
abstract: 5-Fluorouracil (5-FU) is an anticancer drug and is considered a gold standard for the treatment of skin cancer. At present, topical chemotherapy with 5-FU is associated with the limitations of poor skin permeation, retention at target site, and skin irritation potential. In the present study, an attempt has been made to develop an ethosome-based topical gel formulation (ethogel) for skin targeting of 5-FU. The ethosomal formulation was prepared using the classical dispersion method, and loading of 5% w/w of the drug was optimized to the commercial strength of marketed 5-FU cream. Carbopol 934P was used as a gel former in 0.5, 0.75, 1.0, and 1.5% w/w concentration for preparation of ethosome-based ethogel formulation. The ethogel formulation was characterized for viscosity, spreadability, extrudability, and pH. Viscosity of the developed ethogel and that of the marketed formulation was found to be 3070±14.7 and 2870±14.4 cP, respectively. An in-vitro skin permeation and deposition study was carried out across rat skin using the marketed cream and 5-FU drug solution as controls. The amount of drug deposition was found to increase 5.9- and 9.4-fold on treatment with ethogel in comparison with the marketed cream and drug solution, respectively. The result of antitumor activity evaluated using a Cytoselect 96-well cell transformation assay revealed a large reduction in tumor density with treatment with the 5-FU ethogel formulation in comparison with the marketed formulation. A significant reduction in the skin irritation potential of 5-FU ethogel formulation was also found in comparison with that of the marketed formulation as measured by the Draize test. The results of the present study demonstrated ethogel as a better alternative for increasing the local bioavailability of 5-FU in comparison to the marketed formulation.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Puri
authors.forename: Subheet
authors.initials: S
authors.lastname: Jain
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004548:Elasticity; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005782:Gels / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D023422:Skin Irritancy Tests; D013025:Glycine max / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution; D014783:Viscosity
chemical_list: D000179:Acrylates; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D005782:Gels; D010713:Phosphatidylcholines; C453622:carbopol 934P; D005472:Fluorouracil