Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer

• Published in: Pharmaceutics Vol. 13; no. 10; p. 1560
• Main Authors: Gamal, Amr, Saeed, Haitham, El-Ela, Fatma I. Abo, Salem, Heba F.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 26.09.2021; MDPI
• Subjects: Bioavailability; Cholesterol; Drug delivery systems; Efficiency; Ethanol; ethosomes; Nanoparticles; Particle size; Permeability; Skin cancer; Sonidegib; targeting; Transdermal medication; Cairo Egypt; United States > US; Germany; Egypt
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13101560

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.