Rossetti Fábia Cristina, Depieri Lívia Vieira, Praça Fabíola Garcia, Del Ciampo José Orestes, Fantini Márcia C A, Pierre Maria Bernadete Riemma, Tedesco Antônio Cláudio, Bentley Maria Vitória Lopes Badra
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café, s/n, 14040-160, Ribeirão Preto, SP, Brazil.
Instituto de Física, Universidade de São Paulo, SP, Brazil.
Eur J Pharm Sci. 2016 Feb 15;83:99-108. doi: 10.1016/j.ejps.2015.12.003. Epub 2015 Dec 3.
Nanodispersions of liquid-crystalline phases (NLPs) composed of monoolein and oleic acid were chosen as nanocarriers to improve the topical retention of the photosensitizer protoporphyrin IX (PpIX) and thereby optimize photodynamic therapy (PDT) using this photosensitizer. The nanodispersions were characterized by polarized light microscopy, small-angle X-ray diffraction and dynamic light scattering. The stability and encapsulation efficiency (EE%) of the nanodispersions were also evaluated. In vitro and in vivo skin penetration studies were performed to determine the potential of the nanodispersions for cutaneous application. In addition, skin penetration and skin irritancy (in an animal model) after in vivo application were visualized by fluorescence light microscopy. The nanodispersion obtained was characterized as a monodisperse system (150.0 nm) of hexagonal liquid-crystalline phase, which provided a high encapsulation efficiency of PpIX (88%) that remained stable over 90 days of investigation. Skin penetration studies demonstrated that the nanodispersion enhanced PpIX skin uptake 11.8- and 3.3-fold (in vitro) and 23.6- and 20.8-fold (in vivo) compared to the PpIX skin uptake of control formulations, respectively. In addition, the hexagonal phase nanodispersion did not cause skin irritation after application for two consecutive days. Overall, the results show that the nanocarrier developed is suitable for use in topical PDT with PpIX.
由单油酸甘油酯和油酸组成的液晶相纳米分散体（NLPs）被选作纳米载体，以提高光敏剂原卟啉IX（PpIX）的局部保留率，从而优化使用该光敏剂的光动力疗法（PDT）。通过偏光显微镜、小角X射线衍射和动态光散射对纳米分散体进行了表征。还评估了纳米分散体的稳定性和包封率（EE%）。进行了体外和体内皮肤渗透研究，以确定纳米分散体用于皮肤给药的潜力。此外，通过荧光显微镜观察了体内给药后的皮肤渗透和皮肤刺激性（在动物模型中）。所获得的纳米分散体被表征为六方液晶相的单分散体系（150.0 nm），其对PpIX具有较高的包封率（88%），在90天的研究期间保持稳定。皮肤渗透研究表明，与对照制剂的PpIX皮肤摄取相比，纳米分散体分别使PpIX的皮肤摄取在体外提高了11.8倍和3.3倍，在体内提高了23.6倍和20.8倍。此外，连续两天应用后，六方相纳米分散体未引起皮肤刺激。总体而言，结果表明所开发的纳米载体适用于与PpIX联合的局部PDT。
