OPTIMIZATION AND CHARACTERIZATION OF 5-FLUOROURACIL TRANSETHOSOMES FOR SKIN CANCER THERAPY USING RESPONSE SURFACE METHODOLOGY.

Abstract

The purpose of the present study was to develop, optimize and characterize 5-Fluorouracil transethosomes for skin cancer targeting. 5-Fluorouracil transethosomes were prepared by cold method using phospholipon 90G as the lipid and sodium cholate as edge activator. The size reduction was done by probe sonication. Central composite design was used for optimization procedure with different concentration of phospholipon 90G and sodium cholate as independent variables. The response variables selected were particle size and entrapment efficiency. Particle size and entrapment efficiency depends on the quantity of the above independent variables. Mathematical equation and response surface plots were used to relate the dependent and independent variables. The optimized model predicted a particle size of 57nm and entrapment efficiency of 92.06%. Transethosomes proved to be superior in terms of, amount of drug permeated in the skin as compared to conventional 1% flonida cream. The results suggests that transethosomes are efficient carriers for transdermal delivery of 5-Fluorouracil. Copy Right, IJAR, 2018,. All rights reserved. Introduction:-5-fluorouracil is a small, membrane permeable hydrophilic drug and to retain this molecule in the aqueous compartment of liposomes has been difficult to achieve. Conventional 5-FU is available in several strengths like 1%, 2% and 5% solutions and 1% and 5% creams for topical use. The conventional creams are not able to penetrate into the deeper layers of tumors [1] . Transdermal delivery is an attractive alternative to oral delivery of drugs as it can overcome various shortcomings of oral drug delivery. It avoids first pass metabolism of bioactives, avoids dose dumping, lower fluctuations in plasma drug levels, gastrointestinal side effects and high patient compliance. The skin acts as an excellent barrier for molecular transport, and this is the rationale for the transdermal delivery. Most conventional methods of drug intake namely oral route is not feasible and thus alternative routes must be sought. Intravenous delivery of medicaments avoids many shortcomings such as gastrointestinal and hepatic metabolism but its invasive and apprehensive nature, particularly for chronic administration has encouraged alternative strategies. The transdermal route offers several advantages including large and readily accessible surface area of 1–2 m for drug absorption,ease of application and termination of therapy. Better technologies have evolved for delivering of drug molecules over the past few years. It provides sustained release for drugs with short biological half-lives which requires frequent oral or parenteral administration and controlled release for drugs with narrow therapeutic index [2] . In this investigation, ultradeformable vesicles was developed to deliver 5-FU as an alternative vehicle for topical drug delivery to oral conventional dosage form. 5-FU was the most suitable drug to deliver across the skin for the