Optimization and Formulation of Fucoxanthin-Loaded Microsphere (F-LM) Using Response Surface Methodology (RSM) and Analysis of Its Fucoxanthin Release Profile
Optimization and Formulation of Fucoxanthin-Loaded Microsphere (F-LM) Using Response Surface Methodology (RSM) and Analysis of Its Fucoxanthin Release Profile
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DOI：
10.3390/molecules24050947
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发表时间：
2019-03-01
期刊：
影响因子：
4.6
通讯作者：
Almansori, Bubaker B. Hamad
中科院分区：
文献类型：
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作者：
Jaswir, Irwandi;Noviendri, Dedi;Almansori, Bubaker B. Hamad
岩藻黄素具有有趣的抗癌活性，但不溶于水，阻碍了其作为药物的用途。微囊化被用作改善药物递送的技术。本研究旨在制备岩藻黄质微球（F-LM）用于H1299肿瘤细胞系的抗癌治疗，并优化粒径（PS）和包封率（EE）。采用响应曲面法（RSM），以聚乙烯醇（PVA）、聚（D，L-乳酸-羟基乙酸）共聚物（PLGA）和岩藻黄素浓度为三个因素，设计了面心中心复合设计（FCCCD）。采用改进的复乳溶剂蒸发法制备了F-LM。对F-LM的释放曲线、释放动力学和降解模式进行了表征。最佳的F-LM PS和EE分别为9.18 μ m和33.09%，具有良好的表面形态，从0.5%（w/v）PVA，6.0%（w/v）PLGA，200 μ g/mL岩藻黄素配方在20，500 rpm的均化速度。PVA浓度是影响PS的最显著因素（p < 0.05）。同时，EE显着影响的三个因素之间的交互作用：PVA，PLGA，和岩藻黄质。体外释药曲线显示岩藻黄素在第1 h有较高的突释率（38.3%），随后进入持续释放阶段（79.1%），2个月内释放度最高。释放动力学遵循主要由Higuchi模型控制的扩散模式。基于F-LM表面上的表面形态变化的生物降解性研究表明，形态在第一个小时内发生变化，并且F-LM在2个月内完全降解。FCCCD设计下的响应面改善了最低和最高响应之间的差异，F-LM的PS和EE的观测值和预测值之间具有良好的相关性。
Fucoxanthin has interesting anticancer activity, but is insoluble in water, hindering its use as a drug. Microencapsulation is used as a technique for improving drug delivery. This study aimed to formulate fucoxanthin-loaded microspheres (F-LM) for anticancer treatment of H1299 cancer cell lines and optimize particle size (PS) and encapsulation efficiency (EE). Using response surface methodology (RSM), a face centered central composite design (FCCCD) was designed with three factors: Polyvinylalcohol (PVA), poly(D,L-lactic-co-glycolic acid) (PLGA), and fucoxanthin concentration. F-LM was produced using a modified double-emulsion solvent evaporation method. The F-LM were characterized for release profile, release kinetics, and degradation pattern. Optimal F-LM PS and EE of 9.18 mu m and 33.09%, respectively, with good surface morphology, were achieved from a 0.5% (w/v) PVA, 6.0% (w/v) PLGA, 200 mu g/mL fucoxanthin formulation at a homogenization speed of 20,500 rpm. PVA concentration was the most significant factor (p < 0.05) affecting PS. Meanwhile, EE was significantly affected by interaction between the three factors: PVA, PLGA, and fucoxanthin. In vitro release curve showed fucoxanthin had a high burst release (38.3%) at the first hour, followed by a sustained release stage reaching (79.1%) within 2 months. Release kinetics followed a diffusion pattern predominantly controlled by the Higuchi model. Biodegradability studies based on surface morphology changes on the surface of the F-LM, show that morphology changed within the first hour, and F-LM completely degraded within 2 months. RSM under FCCCD design improved the difference between the lowest and highest responses, with good correlation between observed and predicted values for PS and EE of F-LM.