Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Dominique Pepe,1 Vanessa FM Carvalho,2 Melissa McCall,1 Débora P de Lemos,2 Luciana B Lopes1,2 1Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 2Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Abstract: In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. All MEs displayed nanometric size (32.3–40.7 nm) and slight positive zeta potential (+4.1 mV to +6.8 mV). Skin penetration of paclitaxel from the MEs was assessed for 1–12 hours using porcine skin and Franz diffusion cells. Among the PTD-containing formulations, paclitaxel skin (stratum corneum + epidermis and dermis) penetration at 12 hours was maximized with ME-T, whereas ME-TAT provided the lowest penetration (1.6-fold less). This is consistent with the stronger ability of ME-T to increase transepidermal water loss (2.4-fold compared to water) and tissue permeability. The influence of PTD addition on the ME irritation potential was assessed by measuring interleukin-1α expression and viability of bioengineered skin equivalents. A 1.5- to 1.8-fold increase in interleukin-1α expression was induced by ME-T compared to the other formulations, but this effect was less pronounced (5.8-fold) than that mediated by the moderate irritant Triton. Because ME-T maximized paclitaxel cutaneous localization while being safer than Triton, its efficacy was assessed against basal cell carcinoma cells and a bioengineered three-dimensional melanoma model. Paclitaxel-containing ME-T reduced cells and tissue viability by twofold compared to drug solutions, suggesting the potential clinical usefulness of the formulation for the treatment of cutaneous tumors. Keywords: microemulsion, nanocarriers, protein transduction domains, paclitaxel, skin, transderma

Práticas baseadas em evidências publicadas no Brasil: identificação e análise de suas vertentes e abordagens metodológicas

Revisão integrativa de estudos brasileiros sobre práticas baseadas em evidências (PBE) em saúde, publicados em periódicos ISI/JCR, nos últimos 10 anos. O objetivo foi identificar as especialidades que mais realizaram estes estudos, seus enfoques e abordagens metodológicas. A partir de critérios de inclusão, foram selecionados 144 trabalhos. Os resultados indicam que a maior quantidade de estudos feitos em PBE foram sobre infância e adolescência, infectologia, psiquiatria/saúde mental e cirurgia. Os enfoques predominantes foram prevenção, tratamento/reabilitação, diagnóstico e avaliação. As metodologias mais empregadas foram revisão sistemática sem ou com metanálise, revisão de protocolos ou síntese de estudos de evidências já disponíveis, e revisão integrativa. Constata-se forte expansão multiprofissional da PBE no Brasil, contribuindo para a busca de práticas mais criteriosas pela reunião, reconhecimento e análise crítica dos conhecimentos produzidos. O estudo contribui também para a própria análise dos modos de fazer pesquisa e novas possibilidades de investigação