Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer

Skin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.

TOPICAL DELIVERY OF QUERCETIN LOADED TRANSFERSOMES FOR WOUND TREATMENT: IN VITRO AND IN VIVO EVALUATION

Objective: To design topical Quercetin (Qc)-loaded transfersomes (TFs) for wound treatment. Methods: Qc-loaded TFs were prepared by thin-film hydration technique using 2241full factorial design and the optimum formula was selected. In vivo skin, deposition and cutaneous wound induction studies were performed for four groups of male wistar rats. At the end of the experiment, biochemical parameters were measured in the healed tissues (total proteins (TP), total antioxidant capacity (TAC), glutathione reductase (GSH), nitric oxide (NO), and malonaldehyde (MDA). Two in vivo histopathological experiments using male wistar rats were performed; the first study was done for the healed tissues of the above experiment and the second was to confirm the safety of formulations. Results: Qc optimum TFs (F6) showed EE% of 91.1%, PS of 695.35 nm, PDI of 0.592, and ZP of-11.1 mV, and spherical shape. In vivo skin deposition study showed that drug percentage retained in the skin from Qc optimum TFs was significantly higher than that from Qc suspension and Qc liposomes (p<0.05). There was no significant difference in the values of TP, TAC and MDA between the treated groups (p>0.05). GSH in TFs treated groups was significantly higher than the other groups (p<0.05) while NO in TFs treated groups was significantly lower than the other treated groups (p<0.05). Histopathological experiments showed that wounds treated by TFs healed better than those treated by both liposomes and Qc suspension. Conclusion: Qc-loaded TFs can be used as successful drug-delivery system for wound healing.