Tailoring of berberine loaded transniosomes for the management of skin cancer in mice

Dermal products are essential categories of drug delivery systems, and their application is getting more common. The reason for preparing transniosomes (TN) was to enhance the permeability of berberine (BBR) and to deliver the encapsulated BBR specifically to a localized area of the skin. The TN exhibited higher efficacy than the niosomes in terms of skin penetration and incorporation of TN into gel could also upsurge the thickness of formulation and thereby promote the residence phase of optimized formulation at the application site. The goal of the present research was to optimize TN for accentuated dermal delivery of BBR. The optimization of BBR-loaded TN was done using the "Box-Behnken design". The optimized formulation was characterized for vesicles size, entrapment efficiency (%) and in vitro BBR release. Additionally, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and dermatokinetic study were performed for further evaluation of BBR-loaded optimized TN formulation. The optimized BBR-TN formulation presented sealed lamellar shaped vesicles, with vesicles size of 74.05 +/- 1.55 nm, entrapment efficiency of 82.54 +/- 0.54% and in vitro release of 61.44 +/- 1.97%. The obtained CLSM images of mice's skin clearly exemplified that the rhodamine B-loaded TN gel disseminated to deeper layer than the control (rhodamine B-hydroethanolic solution). Further, the BBR-TN gel treated mice skin showed C-Skin max and AUC(0-t) of 132.23 mu g/cm(2) (epidermis) and 683.07 mu g/cm(2)h (epidermis) in comparison to C-Skin max and AUC(0-t) of 59.86 mu g/cm(2) (epidermis) and 321.41 mu g/cm(2)h (epidermis) presented by BBR conventional gel. The in-vivo study showed that the BBR-TN gel pre-treatment mitigates the tumor multiplicity and prevented the tumor size growth in mice. Further the BBR-TN gel formulation found to be safer for skin application as depicted by skin irritation study performed on mice. The present investigation validated that the prepared TN is a valuable drug carrier system for dermal delivery of BBR for the management of skin cancer in animal model.