Comparative study of transfersomes, liposomes, and niosomes for topical delivery of 5-fluorouracil to skin cancer cells

Abstract

Topical 5-fluorouracil (5-FU) is used for the treatment of actinic keratosis and nonmelanoma skin cancer. Unfortunately, 5-FU per se shows a poor percutaneous permeation, thus reducing its anticancer effectiveness after topical administration. Therefore, we have constructed transfersomes, liposomes, and niosomes of 5-FU for topical applications in this investigation. Transfersomes were prepared by the solvent evaporation method, whereas liposomes and niosomes were constructed by reverse-phase evaporation method. The nanovesicles were characterized for particle size, shape, zeta potential, viscosity, entrapment efficiency, deformability, in-vitro permeation release, and kinetics and retention. Cytotoxicity study was carried out on HaCaT cells. Transfersomes (153.2 ± 10.3 nm), liposomes (120.3 ± 9.8 nm), and niosomes (250.4 ± 8.6 nm) were produced with a maximum entrapment efficiency of 82.4 ± 4.8, 45.4 ± 3.3, and 43.4 ± 3.2%, respectively. Moreover, transmission electron microscopy and atomic force microscopy assure the smooth and spherical shape of nanovesicles. Skin permeation and retention showed better permeability and retention than the nonvesiculized dosage form. The IC50 value of transfersomes (1.02 μmol/l), liposomes (6.83 μmol/l), and niosomes (9.91 μmol/l) was found to be far less than 5-FU (15.89 μmol/l) at 72 h. 5-FU-loaded transfersomes were found to be most cytotoxic on the HaCaT cell line in comparison with liposomes and niosomes. We concluded that vesiculization of 5-FU not only improves the topical delivery, but also enhances the cytotoxic effect of 5-FU. We have presented here a viable formulation of 5-FU for the management of actinic keratosis and nonmelanoma skin carcinoma.

Delivery of drugs applied topically to the skin

“…Vaccines, 5-fluorouracil, IL-2 and IFN-α [149][150][151] SECosomes or nanosomes Mixture of surfactant, ethanol and cholesterol siRNA [121] SLNs Produced with one single solid lipid and surfactants, with perfect crystalline lattice CoQ-10, glucocorticoids, minoxidil and oxybenzone [152][153][154][155] NLCs Produced with solid and liquid lipids and surfactants, with distorted crystalline lattice Targeted tumor delivery, phospholipase A2 inhibitors, benzocaine, lidocaine and psoriasis treatment [156][157][158][159] Polymeric nanoparticles Consist of micro-and nano-spheres or capsules developed to control the release of the entrapped drug Chlorhexidine, indomethacin, melatonin and poorly soluble drugs [160][161][162][163] ALA: Aminolevulinic acid; NLC: Nanostructured lipid carrier; SECosome: Surfactant-ethanol-cholesterol-osome; SLN: Solid lipid nanoparticle.…”

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

“…Due to the unfavorable skin permeation profile of 5-fluorouracil in conventional formulations, there has been an increased interest in the use of drug delivery systems to deliver 5-fluorouracil into the deeper layers of the skin. Research has been carried out on the topical delivery of 5-fluorouracil using drug delivery systems such as ethosomes (12) niosomes, liposomes, transfersomes (13), and nanogels (14). In these studies, it showed that the drug delivery systems resulted in an increase in either the flux or retention of API in the skin layers.…”

Transfersomes as versatile and flexible nano-vesicular carriers in skin cancer therapy: the state of the art

“…The topical application of transfersome-entrapped anticancer drug is described by a few research groups. Skin delivery of 5-fluorouracil (5-FU) [32,33,34], methotrexate, and bleomycin has been evaluated by many researchers. Edge activators are often single chain surfactant that destabilizes lipid bilayers of the vesicles and provides a flexible membrane, eventually making transfersomes highly flexible.…”

“…The in vivo results concluded that vesiculization of 5-FU not only improves the topical delivery, but also enhances the cytotoxic effect of 5-FU [87]. An instance of transfersomal gel containing 5-FU provided efficient results against the treatment for AK and non-melanoma skin carcinoma, which showed up to a twofold increase of transdermal release in contrast to other marketed formulations [88].…”

“…Cytotoxicity study was carried out on HaCaT cellsDimiristoylphosphatidylcholine,dipalmitoyl-phosphatidylcholine,cholesterol, sodium cholateThe IC 50 value of transfersomes (1.02 μmol/l), liposomes (6.83 μmol/l), and niosomes (9.91 μmol/l) was found to be far less than 5-FU (15.89 μmol/l) at 72 h. 5-FU-loaded transfersomes were found to be most cytotoxic on the HaCaT cell line in comparison with liposomes and niosomes. The results concluded that vesiculization of 5-FU not only improves the topical delivery, but also enhances the cytotoxic effect of 5-FU[115]Raloxifene hydrochloride–In this study a researcher developed and optimized raloxifene hydrochloride-loaded nanotransfersomes for transdermal delivery, in order to overcome the poor bioavailability of the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental designPhospholipon® 90G, sodium deoxycholateRaloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25 ± 1.50 and 9.25 ± 2.40, respectively, when compared with conventional liposomes, and an ethanolic solution.…”