Background and Objective: Non-melanoma Skin Cancer (NMSC) is the most common malignancy
found in humans and currently 2-3 million cases occur globally and occur in the persons with
light skin and less melanin content. It often appears as a painless, raised area of skin, which may be
shiny or with the hard lump with a scaly top, but may also form an ulcer which may spread to other
parts of the body. Nonsurgical management of NMSC could be a viable and effective treatment option,
however, permeation of hydrophilic drugs such as 5-fluorouracil through the skin may hamper the success
of topical application approach. Therefore, the aim of this work was to incorporate 5-fluorouracil
in ethosomes using a Fractional Factorial Design in order to improve its skin permeation.
Methods: The 5-fluorouracil ethosomes were prepared by cold method through 25-2 Fractional factorial
design in which amount of Phospholipon®90H(A), Drug(B), Propylene Glycol(C), Ethanol(D) and
Sonication time(E) was selected as independent variables and vesicle size(X1) and %Entrapment Efficiency
(%EE)(X2) as dependent variables.
Results: All the batches exhibited the vesicle size and %EE in the range of 74.43-653.8 nm and 34.64-
50.94%. The optimized batch of ethosomes (K3) exhibited 229.6nm vesicle size, 55.41%EE and
14.9mV zeta potential indicating suitability for skin permeation and stability of the formulation. During
%In-vitro drug release study, Batch K3 indicated 69.30% and 59.18% of drug release after 12 hours as
compared to 82.84% and 91.8% of pure drug in acetate Buffer pH 6.0 and phosphate buffer pH 7.4 respectively
indicating the sustained release of drug.
Conclusion: Thus, the prepared formulation might have potential applications of delivering the drug in
controlled manner directly to the site of action by overcoming the limitations of conventional formulations
and by enhancing drug penetration to deeper layers of skin, by reduce dosing frequency and thus
with improved bioavailability for the treatment of non-melanoma skin cancer.