Abstract: The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. Herein, an investigation proceeded to explore the usefulness of nano lipid vesicles (transethosomes) (TES) of CXB to permit penetration of considerable quantities of the drug for curing skin cancer. The prepared nanovesicles were distinguished for drug
encapsulation efficiency, vesicle size, PDI, surface charge, and morphology. In addition, FT-IR and DSC analyses were also conducted to examine the influence of vesicle components. The optimized formulation was dispersed in various hydrogel bases. Furthermore, in vitro CXB release and ex vivo permeability studies were evaluated. A cytotoxicity study proceeded using A431 and BJ1 cell lines. The expression alteration of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and DNA damage and fragmentation using qRT-PCR and comet assays were also investigated. Optimized
CXB-TES formulation was spherically shaped and displayed a vesicle size of 75.9 ± 11.4 nm, a surface charge of - 44.7 ± 1.52 mV, and an entrapment efficiency of 88.8 ± 7.2%. The formulated TES-based hydrogel displayed a sustained in vitro CXB release pattern for 24 h with an enhanced flux and permeation across rat skin compared with the control (free drug-loaded hydrogel). Interestingly, CXB-TES hydrogel has a lower cytotoxic effect on normal skin cells compared with TES suspension and CXB powder. Moreover, the level of expression of the CDKN2A gene was significantly (p ≤ 0.01, ANOVA/Tukey) decreased in skin tumor cell lines compared with normal skin cell lines, indicating that TES are the suitable carrier for topical delivery of CXB to the cancer cells suppressing their progression. In addition, apoptosis demonstrated by comet and DNA fragmentation assays was evident in skin cancer cells exposed to CXB-loaded TES hydrogel formulation. In conclusion, our results illustrate that CXB-TES-loaded hydrogel could be considered a promising carrier and effective chemotherapeutic agent for the management of skin carcinoma.

Herein, we report a facile preparation of vertically oriented reduced graphene oxide sheets (VrGO) supported on
a palladium nanoparticles-decorated graphite electrode. The electrode is fabricated by a simple two electrodeposition steps method. The designed electrode BEFD&VrGO@PdNPs successfully provides an open structure of rGO layer exposing palladium nanoparticles (PdNPs) to the solution, leading to formation of a uniform distributed vertically oriented rGO (VrGO) due to the high surface area of palladium-decorated PGE substrate. The fabricated electrode was successfully used for determination of sorafenib (SOR); an anti-cancer drug. Using square wave voltammetric method (SWV), the fabricated electrochemical sensor succeeds to monitor the electro-oxidation of SOR with a low limit of detection of 9.9 x10? 10 M and ultrahigh sensitivity of 237 μA nM? 1cm? 2 over a linear concentration range of 3–120 10? 9 M with an excellent correlation coefficient. Additionally, the performance of the modified electrode has been successfully tested by real-time monitoring of SOR in pharmaceutical tablets, human plasma, and human urine without any interference from complex matrices.