A timescale-guided microfluidic synthesis of tannic acid-FeIII network nanocapsules of hydrophobic drugs.
A timescale-guided microfluidic synthesis of tannic acid-FeIII network nanocapsules of hydrophobic drugs.
复制标题
DOI：
10.1016/j.jconrel.2023.04.024
复制
发表时间：
2023-04
期刊：
影响因子：
--
通讯作者：
Ying-yan Shen;Simseok A. Yuk;Soonbum Kwon;H. Tamam;Y. Yeo;B. Han
中科院分区：
文献类型：
--
作者：
Ying-yan Shen;Simseok A. Yuk;Soonbum Kwon;H. Tamam;Y. Yeo;B. Han
许多药物水溶性差，生物利用度低。金属-酚醛网络（Metal-phenolic network，MPN）是一种亲水性薄层，如单宁酸（Tannic acid，TA）-FeIII网络，近年来被用于包裹疏水性药物以提高其生物利用度。然而，合成各种疏水药物的纳米胶囊并以连续方式扩大生产仍然具有挑战性。在这里，我们提出了一种微流控合成方法，连续生产TA-FeIII网络疏水药物纳米胶囊。我们假设只有当微流体混合时间尺度短于药物的成核时间尺度时，纳米胶囊才能连续形成。这一假设在三种疏水性药物-紫杉醇、姜黄素和维生素D上进行了测试，这些药物具有不同的溶解度和成核时间尺度。通过成功预测合成结果验证了所提出的机制。微流体合成的纳米胶囊具有100-200 nm的良好控制的尺寸，40- 70%的高载药量，每个通道的通量高达70 mg hr− 1。进一步评价了释放动力学、细胞摄取和细胞毒性。研究了涂层组分对纳米胶囊性能的影响。报道了纳米胶囊的Fe含量。还测试了纳米胶囊在不同温度和pH下的稳定性。结果表明，本方法可以提供一个定量的指导方针，预测性地设计一个连续的合成方案，疏水药物封装通过MPN纳米胶囊与放大能力。
Many drugs are poorly water-soluble and suffer from low bioavailability. Metal-phenolic network (MPN), a hydrophilic thin layer such as tannic acid (TA)-FeIIInetwork, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize nanocapsules of a wide variety of hydrophobic drugs and to scale up the production in a continuous manner. Here, we present a microfluidic synthesis method to continuously produce TA-FeIIInetwork nanocapsules of hydrophobic drugs. We hypothesize that nanocapsules can continuously be formed only when the microfluidic mixing timescale is shorter than the drug's nucleation timescale. The hypothesis was tested on three hydrophobic drugs - paclitaxel, curcumin, and vitamin D with varying solubility and nucleation timescale. The proposed mechanism was validated by successfully predicting the synthesis outcomes. The microfluidically-synthesized nanocapsules had well-controlled sizes of 100–200 nm, high drug loadings of 40–70%, and a throughput of up to 70 mg hr−1per channel. The release kinetics, cellular uptake, and cytotoxicity were further evaluated. The effect of coating constituents on nanocapsule properties were characterized. Fe content of nanocapsules was reported. The stability of nanocapsules at different temperatures and pHs were also tested. The results suggest that the present method can provide a quantitative guideline to predictively design a continuous synthesis scheme for hydrophobic drug encapsulation via MPN nanocapsules with scaled-up capability.