Abstract:
New topical gel formulations based on sodium alginate and hyaluronic acid containing AS1411 aptamer-functionalized
polymeric nanocapsules loaded with an antitumoral drug (5-Fluorouracil) were designed as an innovative
approach for the skin cancer treatment. Several important analyses were used to characterize these
obtained topical gel formulations, namely: rheological tests, permeation assays across Strat-M® artificial membrane,
ex-vivo permeation assays across chicken skin membrane, haemolysis tests, skin irritation tests, in vitro
cytotoxicity assay on human basal carcinoma cells and in vivo tests. Rheological tests revealed that apparent
viscosity decreases with the increase of the shear rate, for analyzed samples, which demonstrates a shear
thinning behavior. Low levels of hemolysis values which ranged between 0.03 and 0.55% suggested that the
tested formulations did not induce red blood cell lysis.. The gel formulations containing nanocapsules loaded
with 5-FU proved to be non-irritant. Furthermore, by study the ex-vivo diffusion properties across the chicken
skin membrane, it was proved that nanoencapsulation enhance the permeability properties of 5-FU. In vitro
cytotoxicity assay on TE 354.T (ATCC® CRL-7762™) human basal carcinoma cell line showed that the obtained
formulations loaded with 5-Fluorouracil manifest an important cytotoxic effect. Finally, the presence of
Langerhans CD68 cells-positive in the epidermis and epithelial sheath of dermal hair follicles suggests a specific
activation, migration and retrieval of nanoparticles by these cells. Following the results obtained in this study we
can appreciate that the obtained topical gel formulations have a favourable biosafety and good antitumor effects
which makes them attractive for skin cancer treatment.
