Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention.

Mengbing Chen,Kristen M Kelly,Vijaykumar Nekkanti,Ayaz Shahid,Frank L Meyskens,Steven Yeung,Md Abdullah Shamim,Jeffrey Wang,Ying Huang,Bradley T Andresen

doi:10.3390/pharmaceutics12121151

Mengbing Chen, Kristen M Kelly + Show 8 more

Open Access

https://doi.org/10.3390/pharmaceutics12121151

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Abstract

The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis.

Highlights

Skin cancer, consisting of basal- and squamous-cell carcinoma and melanoma, is the most common type of cancer in the U.S and the world [1]
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Studies on a 3D reconstituted human skin model confirmed that topical F18 produced photoprotective effects against UV-induced DNA damage, inflammation, and apoptosis

Summary

Introduction

Skin cancer, consisting of basal- and squamous-cell carcinoma (non-melanoma skin cancer) and melanoma, is the most common type of cancer in the U.S and the world [1]. Solar ultraviolet (UV) radiation, mainly consisting of UVA (320,400 nm) and UVB (290,320 nm), increases the risk of skin cancer [2]. Previous studies have indicated that the β-blocker carvedilol, commonly used to manage cardiovascular disorders such as hypertension and heart failure, showed promising activity in preventing chemical carcinogen and UV-induced skin carcinogenesis in vitro and in vivo [3,4]. Further supporting a role of carvedilol in cancer prevention, a population-based cohort study of 6771 individuals demonstrated that long-term use of carvedilol was associated with a reduced risk of several types of cancer [6]

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