Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery.
Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery.
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DOI：
10.1155/2017/4759839
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发表时间：
2017
影响因子：
--
通讯作者：
John V
中科院分区：
文献类型：
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作者：
Subbiah N;Campagna J;Spilman P;Alam MP;Sharma S;Hokugo A;Nishimura I;John V
基于磷脂的可变形纳米囊泡（dnv）具有灵活的形状，提供了一种适应性强且简便的方法来封装各种类型的治疗药物，并促进局部透皮给药，同时最大限度地减少全身暴露。在这里，我们报告了使用微流控反应器合成DNV，并表明改变输入参数，如流速以及摩尔和流速比，可以提高药物的包载效率，并允许微调DNV的大小、弹性和表面电荷。为了确定dnv包膜药物经皮递送到局部部位的能力，我们合成、表征并测试了携带荧光标记的亲水性双膦酸盐药物AF-647唑来膦酸盐（AF647-Zol）的dnv。将AF647-Zol dnv冻干，重悬，并局部贴敷于小鼠颅骨皮肤。高分辨率荧光成像和共聚焦显微镜显示，与不可变形的纳米囊泡（NVs）或含水药物溶液相比，dnv对目标组织（颅骨）的封装有效载荷递送显著增加。有趣的是，NV的递送并不优于药物水溶液。我们的研究表明，微流控反应器合成的dnv产率高，包封效率高，重现性好，储存后稳定性好，是一种有效的局部透皮给药载体。
Phospholipid-based deformable nanovesicles (DNVs) that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol). AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs) or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.