Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm2/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.

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Tamoxifen citrate (TXC) is commonly indicated to prevent cell multiplication and development of breast cancer. However, it is usually associated with limited activity and development of toxicity and resistance. This study aimed to describe an in situ pH-responsive niosomes as a carrier for localized and sustained delivery of TXC. The thin film hydration method was utilized to produce TXC niosomes using sorbitan monostearate and cholesterol of 1:1 Molar ratio. The produced formula displayed nano-spherical shape with entrapment efficiency (EE) of 88.90 ± 0.72% and drug release of 49.2 ± 1.51% within 8 h. This formula was incorporated into chitosan/glyceryl monooleate (CH/GMO) as a localized in situ pH-responsive hydrogel delivery system. Different formulae were produced by Design-Expert software based on user-defined response surface design utilizing different chitosan concentration (A) and GMO concentration (B) characterized for mean viscosity (R) and in vitro release studies (R). The results displayed that R was significantly antagonistic with both of A and B while R was significantly synergistic with both of them. The optimum formula was selected and capped with gold as an ideal candidate for computed tomography (CT) to evaluate the efficacy and tissue distribution of TXC utilizing Ehrlich carcinoma mice model. The optimum formula showed localized TXC in a tumour and consequently a significant anti-tumour efficacy compared with free TXC. Based on these outcomes, the novel in situ pH-responsive TXC-loaded noisome could be a promising formula for the efficient treatment of breast cancer.