Optimization of Acetalated Dextran-Based Nanocomposite Microparticles for Deep Lung Delivery of Therapeutics via Spray-Drying.
Optimization of Acetalated Dextran-Based Nanocomposite Microparticles for Deep Lung Delivery of Therapeutics via Spray-Drying.
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DOI：
10.1016/j.xphs.2017.07.022
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发表时间：
2017-12
影响因子：
3.8
通讯作者：
Zimeng Wang;Samantha A. Meenach
中科院分区：
文献类型：
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作者：
Zimeng Wang;Samantha A. Meenach
纳米复合微粒（nCmP）系统在肺部药物递送治疗中的应用具有很大的潜力。这项工作旨在确定最佳的喷雾干燥条件，以制备具有特定药物递送特性的nCmP，包括小的空气动力学直径，nCmP暴露于水溶液时有效的纳米颗粒（NP）再分散，高载药量和低含水量。使用缩醛化葡聚糖（Ac-Dex）形成NP，使用姜黄素作为模型药物，并且甘露醇是nCmP制剂中的赋形剂。使用Design-Expert软件应用Box-Behnken设计进行nCmP参数优化。NP比（NP%）和进料浓度（Fc）是影响nCmP系统的空气动力学直径的重要参数。NP%也是影响载药量的重要参数。Fc是唯一显著影响颗粒含水量的参数。所有的nCmP系统可以完全再分散到父NPs，表明在设计范围内，没有任何因素对该属性有影响。制备具有小空气动力学直径、NP再分散、低水含量和高载药量的nCmP的最佳喷雾干燥条件为80%NP %、0.5%Fc和低于130°C的入口温度。
Nanocomposite microparticle (nCmP) systems exhibit promising potential in the application of therapeutics for pulmonary drug delivery. This work aimed at identifying the optimal spray-drying condition(s) to prepare nCmP with specific drug delivery properties including small aerodynamic diameter, effective nanoparticle (NP) redispersion upon nCmP exposure to an aqueous solution, high drug loading, and low water content. Acetalated dextran (Ac-Dex) was used to form NPs, curcumin was used as a model drug, and mannitol was the excipient in the nCmP formulation. Box-Behnken design was applied using Design-Expert software for nCmP parameter optimization. NP ratio (NP%) and feed concentration (Fc) are significant parameters that affect the aerodynamic diameters of nCmP systems. NP% is also a significant parameter that affects the drug loading. Fc is the only parameter that influenced the water content of the particles significantly. All nCmP systems could be completely redispersed into the parent NPs, indicating that none of the factors have an influence on this property within the design range. The optimal spray-drying condition to prepare nCmP with a small aerodynamic diameter, redispersion of the NPs, low water content, and high drug loading is 80% NP%, 0.5% Fc, and an inlet temperature lower than 130°C.