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载三氯醋酸曲安奈德固体脂质纳米粒的设计与优化。

Design and Optimization of Solid Lipid Nanoparticles Loaded with Triamcinolone Acetonide.

机构信息

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.

National Interuniversity Consortium of Materials Science and Technology (INSTM)-Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy.

出版信息

Molecules. 2023 Jul 29;28(15):5747. doi: 10.3390/molecules28155747.

Abstract

Principles of quality by design and design of experiments are acquiring more importance in the discovery and application of new drug carriers, such as solid lipid nanoparticles. In this work, an optimized synthesis of solid lipid nanoparticles loaded with Triamcinolone Acetonide is presented using an approach that involves Stearic Acid as a lipid, soy PC as an ionic surfactant, and Tween 80 as a nonionic surfactant. The constructed circumscribed Central Composite Design considers the lipid and nonionic surfactant quantities and the sonication amplitude in order to optimize particle size and Zeta potential, both measured by means of Dynamic Light Scattering, while the separation of unentrapped drug from the optimized Triamcinolone Acetonide-loaded solid lipid nanoparticles formulation is performed by Size Exclusion Chromatography and, subsequently, the encapsulation efficiency is determined by HPLC-DAD. The proposed optimized formulation-with the goal of maximizing Zeta potential and minimizing particle size-has shown good accordance with predicted values of Zeta potential and dimensions, as well as a high value of encapsulated Triamcinolone Acetonide. Experimental values obtained from the optimized synthesis reports a dimension of 683 ± 5 nm, which differs by 3% from the predicted value, and a Zeta potential of -38.0 ± 7.6 mV (12% difference from the predicted value).

摘要

质量源于设计和实验设计原则在新药物载体(如固体脂质纳米粒)的发现和应用中变得越来越重要。在这项工作中,采用涉及硬脂酸作为脂质、大豆卵磷脂作为离子型表面活性剂和吐温 80 作为非离子型表面活性剂的方法,对载有曲安奈德的固体脂质纳米粒的优化合成进行了研究。构建的限定中心复合设计考虑了脂质和非离子型表面活性剂的数量以及超声幅度,以优化粒径和 Zeta 电位,这两者均通过动态光散射进行测量,而从优化的曲安奈德载固体脂质纳米粒制剂中分离未包封的药物则通过尺寸排阻色谱法进行,随后通过 HPLC-DAD 确定包封效率。所提出的优化制剂旨在最大化 Zeta 电位并最小化粒径,与 Zeta 电位和尺寸的预测值以及高含量的包封曲安奈德具有良好的一致性。从优化合成中获得的实验值报告了 683 ± 5nm 的尺寸,与预测值相差 3%,并且 Zeta 电位为-38.0 ± 7.6mV(与预测值相差 12%)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a0/10420805/ef803aa01d42/molecules-28-05747-g001.jpg

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