Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 632, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2022.122580
Keywords
Dermal delivery; 5-Flurouracil; Cannabidiol; Combinatorial therapy; Non-melanoma skin cancer; Nanoparticles
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In this study, a novel combinatorial chemotherapy using nanostructured lipid carrier gel (FU-CBD-NLCs gel) loaded with 5-fluorouracil (5-FU) and cannabidiol (CBD) was developed. The optimized NLCs had an average particle size of 206 nm and a zeta potential of -34 mV. In vitro and ex vivo drug permeation studies demonstrated the effective delivery of both drugs to the skin layers via lipid structured nanocarriers. The prepared FU-CBD-NLCs showed promising effect in vitro cell studies and superior deposition of drugs at the epidermal and dermal layers.
Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers. Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs. In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of nonmelanoma skin cancer.
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