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基于氯铝酞菁/普朗尼克胶束的高效光动力治疗胶体系统

Highly efficient photodynamic therapy colloidal system based on chloroaluminum phthalocyanine/pluronic micelles.

作者信息

Py-Daniel Karen R, Namban Joy S, de Andrade Laise R, de Souza Paulo E N, Paterno Leonardo G, Azevedo Ricardo B, Soler Maria A G

机构信息

Universidade de Brasilia, Laboratório de Nanobiotecnologia, GEM-IB, Brasilia, DF 70910-900, Brazil.

Universidade de Brasilia, Instituto de Fisica, Brasilia, DF 70910-900, Brazil.

出版信息

Eur J Pharm Biopharm. 2016 Jun;103:23-31. doi: 10.1016/j.ejpb.2016.03.028. Epub 2016 Mar 24.

Abstract

Phthalocyanine derivatives comprise the second generation of photosensitizer molecules employed in photodynamic therapy (PDT) and have attracted much attention due to their outstanding photosensitizing performance. Most phthalocyanines are hydrophobic compounds that require association to drug delivery systems for clinical use. In this study, formulations of Pluronic F127 micelles incorporated with chloroaluminum phthalocyanine, or else F127/AlClPc, were produced at optimized conditions aiming at efficient and biocompatible PDT colloidal systems. Absorption/emission spectroscopies, as well as dynamic light scattering were performed to evaluate the optimum conditions for the F127 micelle formation and AlClPc incorporation. The micelles formation was attained with F127 concentrations ranging from 50 to 150mgmL(-1). At these conditions, AlClPc photosensitizer molecules were encapsulated into the hydrophobic micelle core and, therefore, readily solubilized in physiological medium (PBS pH 7.2). Encapsulation efficiency of about 90% resulted from different AlClPc concentrations. Identification of singlet oxygen production by irradiated F127/AlClPc formulations indicated good applicability for PDT. In vitro tests conducted with A549 human lung carcinoma cell line incubated with the F127/AlClPc formulations, at different AlClPc loadings, followed by only 18min of light irradiation (660nm LED, fluence of 25.3J/cm(2)), showed a cellular damage as high as 90% for rather low dosages of AlClPc (0.1-5.0μgmL(-1)). Further, no cytotoxicity occurred on non-irradiated cells. These findings suggest those F127/AlClPc formulations are highly promising for PDT applications, since they are easily prepared and the incubation and irradiation times are significantly shortened.

摘要

酞菁衍生物是光动力疗法(PDT)中使用的第二代光敏剂分子,因其出色的光敏性能而备受关注。大多数酞菁是疏水性化合物,临床使用时需要与药物递送系统结合。在本研究中,在优化条件下制备了负载氯铝酞菁的普朗尼克F127胶束制剂,即F127/AlClPc,旨在构建高效且生物相容的PDT胶体系统。通过吸收/发射光谱以及动态光散射来评估F127胶束形成和AlClPc负载的最佳条件。当F127浓度在50至150mg/mL(-1)范围内时可形成胶束。在这些条件下,AlClPc光敏剂分子被包裹在疏水胶束核心中,因此易于溶解在生理介质(PBS pH 7.2)中。不同AlClPc浓度下的包封效率约为90%。对辐照后的F127/AlClPc制剂产生单线态氧的鉴定表明其在PDT方面具有良好的适用性。用F127/AlClPc制剂在不同AlClPc负载量下孵育A549人肺癌细胞系,随后仅进行18分钟的光照射(660nm LED,光通量为25.3J/cm²),体外试验表明,对于相当低剂量的AlClPc(0.1 - 5.0μg/mL(-1)),细胞损伤高达90%。此外,未辐照的细胞没有发生细胞毒性。这些发现表明,F127/AlClPc制剂在PDT应用方面极具前景,因为它们易于制备,且孵育和照射时间显著缩短。

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