Synthesis of Monodisperse Chitosan Nanoparticles and in Situ Drug Loading Using Active Microreactor
Synthesis of Monodisperse Chitosan Nanoparticles and in Situ Drug Loading Using Active Microreactor
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DOI：
10.1021/acsami.5b05100
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发表时间：
2015-10-21
影响因子：
9.5
通讯作者：
Paknikar, Kishore
中科院分区：
文献类型：
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作者：
Kamat, Vivek;Marathe, Ila;Paknikar, Kishore
壳聚糖纳米颗粒是一种很有前途的药物递送载体。然而，由于离子凝胶在尺寸和物理化学性质上的不均匀性，传统的离子凝胶混合方法限制了它们的应用。因此，对传统微反应器模型和活性微反应器模型进行了详细的理论分析。为此，设计并制造了一种带有磁性微针的聚二甲基硅氧烷微反应器，用于合成单分散壳聚糖纳米颗粒。常规合成的壳聚糖纳米颗粒，以0.5 mg/mL壳聚糖为原料，粒径为250 +/- 27 nm，电荷为+29.8 +/- 8 mV。在相似的条件下，微反应器在400 μ L/min的优化流速下获得了小颗粒（154 +/- 20 nm）。进一步优化后，在0.4 mg/mL的壳聚糖浓度下，获得了具有较高电荷（+39.8 +/- 5 mV）的130 +/- 9 nm颗粒。基于微反应器的良好控制混合产生高度单分散的颗粒，具有可调的性能，包括抗真菌药物包封（80%），释放率和抗念珠菌的有效活性（MIC, 1 μ g/mL）。
Chitosan nanoparticles are promising drug delivery vehicles. However, the conventional method of unregulated mixing during ionic gelation limits their application because of heterogeneity in size and physicochemical properties. Therefore, a detailed theoretical analysis of conventional and active microreactor models was simulated. This led to design and fabrication of a polydimethylsiloxane microreactor with magnetic micro needles for the synthesis of monodisperse chitosan nanoparticles. Chitosan nanoparticles synthesized conventionally, using 0.5 mg/mL chitosan, were 250 +/- 27 nm with +29.8 +/- 8 mV charge. Using similar parameters, the microreactor yielded small size particles (154 +/- 20 nm) at optimized flow rate of 400 mu L/min. Further optimization at 0.4 mg/mL chitosan concentration yielded particles (130 +/- 9 nm) with higher charge (+39.8 +/- 5 mV). The well-controlled microreactor-based mixing generated highly monodisperse particles with tunable properties including antifungal drug entrapment (80%), release rate, and effective activity (MIC, 1 mu g/mL) against Candida.