Topical Skin Cancer Therapy Using Doxorubicin-Loaded Cationic Lipid Nanoparticles and Iontophoresis

Abstract

The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to increase the distribution and tumor penetration of DOX. A double-labeled cationic DOX-SLN composed of the lipids stearic acid and monoolein and a new BODIPY dye was prepared and characterized. The skin distribution and penetration of DOX were evaluated in vitro using confocal microscopy and vertical diffusion cells, respectively. The antitumor potential was evaluated in vivo through the anodic iontophoresis of DOX-SLN in squamous cell carcinoma induced in nude BALB/c mice. The encapsulation of DOX drastically altered the DOX partition coefficient and increased the distribution of DOX in the lipid matrix of the stratum corneum (SC). The association with iontophoresis created high-concentration drug reservoir zones in the follicles of the skin. Although the iontophoresis of a DOX solution increased the penetration of DOX in the viable epidermis by approximately 4-fold, the iontophoresis of cationic DOX-SLN increased the DOX penetration by approximately 50-fold. In vivo, the DOX-SLN iontophoretic treatment was effective in inhibiting tumor cell survival and tumor growth and was accompanied by an increase in keratinization and consequent cell death. These results indicate a strong and synergic effect of iontophoresis with DOX-SLN and provide a potential strategy for the treatment of skin cancer.

Hydrogel increases localized transport regions and skin permeability during low frequency ultrasound treatment

“…DOX is a positively charged drug (pKa = 8.1) with a molecular weight (580 g/mol) similar to the calcein (620 g/mol). However, it is known that DOX strongly interacts with anionic lipids in the SC283839. Figure 4 showed that pre-treatment with LFU and the cationic chitosan coupling medium decreased the amount of DOX recovered from the viable epidermis 2.9-fold.…”

Influência do ultrassom de baixa frequência associado à hidrogéis na permeabilidade da pele e no tratamento tópico do câncer de pele

“…Atualmente, nosso grupo de pesquisa tem investigado o efeito da encapsulação da doxorrubicina (DOX) em NLS visando à administração tópica (Taveira et al, 2012, Taveira et al, 2014, Huber et al, 2015.…”

“…. Recentemente, Huber et al (2015) (Leighton, 1998). Muitos fenômenos interessantes podem ocorrer em solução aquosa devido à oscilação das ondas sonoras, dos quais alguns resultam na maior penetração de fármacos através da pele pela técnica conhecida como sonoforese (Polat et al, 2011a Fonte: Conceitos básicos sobre acústica (2015).…”

Aplicação tópica de lipossomas contendo cetuximabe: efeito do uso de métodos físicos de penetração cutânea no carcinoma celular escamoso de pele

“…al., 2012;BOLFARINI et. al., 2012;LEMOS et al, 2016), antimicrobianos (GAO et al, 2014;PEREZ et al, 2016;JORAHOLMEN et al, 2015) e antitumorais (COSCO et al, 2015;HUBER et al, 2015;PETRILLI et al, 2016 LIMASALE et al, 2015).…”

“…A associação da iontoforese com nanopartículas também já foi avaliada visando o tratamento de tumores cutâneos. A aplicação da iontoforese em nanopartículas lipídicas contendo DOX aumentou a penetração cutânea da DOX (TAVEIRA et al, 2009), o que resultou na regressão do crescimento tumoral do SCC (HUBER et al, 2015).…”