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载姜黄素的低能量纳米乳作为多功能载体的原型:用于不同给药途径的理化和体外特性,对经皮应用很重要。

Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application.

机构信息

Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia.

Institut für Pharmazeutische Technologie, Eberhard-Karls Universität, D-72076 Tübingen, Germany.

出版信息

Int J Pharm. 2018 Oct 25;550(1-2):333-346. doi: 10.1016/j.ijpharm.2018.08.060. Epub 2018 Sep 1.

DOI:10.1016/j.ijpharm.2018.08.060
PMID:30179702
Abstract

The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI < 0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/mL) and FRAP (1.19 ± 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.

摘要

本工作旨在研究并深入表征低能量纳米乳液作为多功能载体,仅略微提及经皮给药。提供了一种循证方法来深入了解其通过自发乳化形成的知识。姜黄素是一种天然来源的化合物,具有潜在的强大治疗作用,被选为模型 API。由于姜黄素具有苛刻的性质(不稳定性、低溶解度、低渗透性),其潜力尚未得到实现。低能量纳米乳液被认为是能够克服所施加障碍的载体。选择包含聚山梨酯 80 和大豆卵磷脂作为稳定剂(9:1,10%)、中链甘油三酯作为油相(10%)和超纯水的配方,将姜黄素以 3 种不同浓度(1、2 和 3 mg/mL)掺入。在 3 个月的监测期间证明了物理化学稳定性(平均粒径:111.3-146.8nm;PDI<0.2;pH:4.73-5.73)。开发的载体中姜黄素的释放遵循 Higuchi 动力学。DPPH(IC50=0.1187 mg/mL)和 FRAP(1.19±0.02 mmol/g)测定证实,姜黄素通过不同机制发挥强大的抗氧化作用,在配方中掺入后没有变化。通过彗星试验估计姜黄素负载制剂的高生物相容性与其抗原毒性活性(保护和修复)一致。需要采用多学科方法来全面表征开发的系统,将其引导到更具体的应用可能性。

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