Skin delivery and in vitro biological evaluation of trans-resveratrol-loaded solid lipid nanoparticles for skin disorder therapies

The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI) and zeta potential were analyzed by dynamic light scattering (DLS). The SLNs were analyzed by scanning electron microscopy (SEM-FEG) and differential scanning calorimetry (DSC). In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than −3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES-loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies21CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informação2011/16888-5; 2012/19568-4; 2013/21500-

Skin Delivery And In Vitro Biological Evaluation Of Trans-resveratrol-loaded Solid Lipid Nanoparticles For Skin Disorder Therapies.

The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI) and zeta potential were analyzed by dynamic light scattering (DLS). The SLNs were analyzed by scanning electron microscopy (SEM-FEG) and differential scanning calorimetry (DSC). In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than -3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES-loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies.2

Avaliação do potencial de carreadores lipídicos nanoestruturados para a administração cutânea de trans-resveratrol

A exposição à radiação solar ultravioleta pode induzir a formação de radicais livres na superfície da pele humana, acelerando o processo de envelhecimento cutâneo, o qual pode ser evidenciado por hiperpigmentação, que traz como consequências aumento na atividade das enzimas melanogênicas, além da liberação de mediadores pró-inflamatórios produzidos pelos queratinócitos, como a interleucina-1α e a endotelina-1 (ET-1). Estudos recentes têm demonstrado que o trans-resveratrol (RES), devido às suas propriedades antioxidantes, despigmentantes e anti-inflamatórias, pode ser um importante aliado no tratamento das alterações decorrentes do fotoenvelhecimento. Dessa forma, sua administração cutânea seria conveniente a fim de localizá-lo no seu sítio de ação. No entanto, algumas de suas propriedades físico-químicas, como limitada solubilidade aquosa e, principalmente, sua alta capacidade de reagir com espécies reativas de oxigênio, dificultam sua eficiência terapêutica tópica, uma vez que possui baixa penetração na pele. Uma alternativa é a sua incorporação em sistemas nanoestruturados, como os carreadores lipídicos nanoestruturados (CLN), que têm sido empregados com sucesso nas áreas farmacêutica e cosmética por apresentarem a capacidade de compartimentalizar, de maneira eficiente, diversos grupos de substâncias ativas, modificando suas propriedades e comportamento em meio biológico. Este projeto teve como objetivo desenvolver e caracterizar, sob o aspecto físico-químico, CLN para a incorporação de RES, de maneira a otimizar sua utilização como agente despigmentante no tratamento do fotoenvelhecimento cutâneo. Foram obtidos CLN empregando os componentes da fase lipídica (estearato de polioxietileno (40) ou behenato de glicerila, triglicérides do ácido cáprico/caprílico e o óleo de rícino) e da fase aquosa (polaxamer 407, nipagin, nipazol e água) pelo uso do homogeneizador de cisalhamento ...Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Quantification of trans-resveratrol-loaded solid lipid nanoparticles by a validated reverse-phase HPLC photodiode array

A new method based on reverse-phase HPLC combined with photodiode array (PDA) was developed to quantify the release of trans-resveratrol (tRES) from solid lipid nanoparticles (SLN). The mobile phase was composed of 75:0:25 (V/V) water/methanol/acetonitrile at 03.5 min, 32.5:30.0:37.5 (V/V) water/methanol/acetonitrile at 3.65.8 min, and 75:0:25 (V/V) water/methanol/acetonitrile at 5.910 min. The flow rate was set at 1.0mL/min, and tRES was detected at the wavelength of 306.6 nm. A concentration range of 1100 µg/mL was used to obtain the linear calibration curve. SLN were produced by ultrasound technique to load 0.1% (wt/wt) of tRES, and the in vitro release of the drug was run in modified Franz diffusion cells. The mean recovery of tRES was found to be 96.84 ± 0.32%. The intra-assay and inter-assay coefficients of variation were less than 5%. The proposed method was applied to in vitro permeability studies, and the Weibull model was found to be the one that best fits the tRES release, which is characterized by a simultaneous lipid chain relaxation and erosion during drug release.The authors wish to acknowledge the financial support from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). The financial support was also received from The Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project M-ERA-NET-0004/2015-PAIRED, co-financed by FEDER, under the Partnership Agreement PT2020. Authors also thank the support of the project: Nutraceutica come supporto nutrizionale nel paziente oncologico; CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio