Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice

Abstract

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.

Ethosomes and their monotonous effects on Skin cancer disruption

“…In vivo studies were based on mice exhibiting chemically induced skin cancer responded significantly to topical treatment of metformin ethosomal gel (Mousa et al, 2022).…”

“…This was demonstrated by presenting a high percentage of the EE%, lowest vesicle size, maximum ZP, and maximum DR% utilising the Box-Behnken design of "a three-level three-factor." When isopropyl alcohol was combined with ethanol to create ethosomes, ethanol's capacity to solubilize lecithin was enhanced, which improved the stability and efficiency of the ethosomes vesicles (Mousa et al, 2022).…”

Unlocking the potential of cosmetic dermal delivery with ethosomes: A comprehensive review

“…Different types of ultracentrifugation exist, including isopycnic centrifugation, Rate-zonal centrifugation, and density gradient centrifugation, each suited to different types of analysis. 31,32 Moreover, the surface tension activity of ethosomes can be measured using the Du Nouy ring tensiometer, which measures surface and interfacial tension. This device uses the ring method, which involves immersing a small ring-shaped sample in the liquid at the interface and measuring the force required to pull the ring from the interface.…”

An evaluation of the effects of ethosomes in the delivery of transdermal drugs

“…Ethosomes are multilamellar nanovesicles that are consisted of phospholipid and ethanol. Ethanol increases the fluidity of phospholipid bilayers, breaks down the SC membrane barrier, and thus enhances penetration (Mousa et al, 2022).…”

“…Classical ethosomes are a development of liposome that contains phospholipids, ethanol, and water. Classical ethosomes had many advantages over classical liposomes in transdermal drug delivery as they had a negative charge which established stability to vesicles and had smaller vesicles to achieve high entrapment efficiency % (Mousa et al, 2022).…”