Topical delivery of Mannose Conjugated-Doxorubicin-Berberine nanostructured lipid carrier gel for skin cancer amelioration: Formulation optimization, in-silico, in-vitro, ex-vivo assessment, and dermatokinetic analysis

Abstract

Mannose-conjugated doxorubicin (DOX) and berberine (BBR) loaded nanostructured lipid carriers (Ma-DB-NLC) topical gel was formulated for skin cancer treatment. DOX is a potent anticancer drug that was combined with BBR to synergize the clinical efficacy of the formulation in skin cancer treatment. The findings of the in-silico study indicated that DOX & BBR were the promising ligands of DNA-Topoisomerase-Ⅱ & p13k, with excellent docking scores. The central composite rotatable design (CCRD) was used to optimize the NLC formulation. The size, PDI, and Zeta Potential (ZP) of Ma-DB-NLC were 202.666 ± 0.907 nm, 0.364 ± 0.002 and −23.666 ± 1.048 mV respectively. The % entrapment efficiency (EE) of prepared formulation was found to be 89.491 ± 1.310 (DOX) and 88.480 ± 1.160 (BBR). Based on the results of permeation studies, Ma-DB-NLC gel has shown better permeation than conventional gel through the mice's skin and Strat-M™ membrane. Moreover, the dermatokinetic study revealed that Ma-DB-NLC gel was found with a better deposition profile. Furthermore, CLSM findings supported the permeation and dermatokinetic results which indicated greater deposition and retention of DOX and BBR into the deeper layer of skin than conventional gel. The prepared Ma-DB-NLC gel was found with better size, ZP, % EE, skin permeation, and deposition than conventional gel for skin cancer amelioration.