RESUMEN
Skin cancer is a widespread type of cancer representing 30% of all cancer types worldwide. Resveratrol (RSV) is an anticancer drug used for skin cancer treatment. Several limitations of RSV such as poor aqueous solubility, first-pass metabolism, and instability limit their topical use. The study aimed to develop and optimize RSV-loaded invasomes for topical administration as well as assess their efficacy in vivo. The optimized RSV-loaded invasomes showed small particle size (208.7 ± 74 nm), PDI (0.3 ± 0.03), high % entrapment efficiency (77.7 ± 6%), and negative zeta potential (-70.4 ± 10.9 mV). They showed an initial burst effect followed by controlled drug release for 24 h. RSV-loaded invasomal gel revealed the highest skin deposition percentage (65%) in ex vivo rat skin, the highest potency (low IC50 of 6.34 µg/mL), and the highest cellular uptake when tested on squamous cancerous cells (SCCs) when compared to other formulations. The antitumor effect of topical RSV-loaded invasomes was also evaluated in vivo in Ehrlich-induced mice models. The results revealed that RSV-loaded invasomal gel exhibited the smallest tumor volume with no signs of organ toxicity indicating its safety in skin cancer treatment. Upregulation of BAX and Caspase-3 gene levels and downregulation of NF-kB and BCL2 protein levels were demonstrated using RT-PCR and ELISA tests, respectively. Interestingly, the present study is the first to develop RSV-loaded invasomal gel for topical skin cancer treatment. According to our results, invasomes are considered promising lipid-based nanosystems for topical RSV delivery having high skin penetration ability and anticancer effect in the treatment of skin carcinoma.