Blakney Anna K, Krogstad Emily A, Jiang Yonghou H, Woodrow Kim A
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Int J Nanomedicine. 2014 Jun 17;9:2967-78. doi: 10.2147/IJN.S61664. eCollection 2014.
Electrospun drug-eluting fabrics have enormous potential for the delivery of physicochemically diverse drugs in combination by controlling the underlying material chemistry and fabric microarchitecture. However, the rationale for formulating drugs at high drug loading in the same or separate fibers is unknown but has important implications for product development and clinical applications.
Using a production-scale free-surface electrospinning instrument, we produced electrospun nanofibers with different microscale geometries for the co-delivery of tenofovir (TFV) and levonorgestrel (LNG) - two lead drug candidates for multipurpose prevention of HIV acquisition and unintended pregnancy. We investigated the in vitro drug release of TFV and LNG combinations from composites that deliver the two drugs from the same fiber (combined fibers) or from separate fibers in a stacked or interwoven architecture. For stacked composites, we also examined the role that fabric thickness has on drug-release kinetics. We also measured the cytotoxicity and antiviral activity of the drugs delivered alone and in combination.
Herein, we report on the solution and processing parameters for the free-surface electrospinning of medical fabrics with controlled microarchitecture and high drug loading (up to 20 wt%). We observed that in vitro release of the highly water-soluble TFV, but not the water-insoluble LNG, was affected by composite microarchitecture, fabric thickness, and drug content. Finally, we showed that the drug-loaded nanofibers are noncytotoxic and that the antiviral activity of TFV is preserved through the electrospinning process and when combined with LNG.
Electrospun fabrics with high drug loading create multicomponent systems that benefit from the independent control of the nanofibrous microarchitecture. Our findings are significant because they will inform the design and production of composite electrospun fabrics for the co-delivery of physicochemically diverse drugs that may be useful for multipurpose prevention.
通过控制基础材料化学和织物微观结构，电纺载药织物在联合递送物理化学性质各异的药物方面具有巨大潜力。然而，在同一根纤维或不同纤维中以高载药量配制药物的基本原理尚不清楚，但对产品开发和临床应用具有重要意义。
使用生产规模的自由表面电纺仪器，我们制备了具有不同微观几何形状的电纺纳米纤维，用于联合递送替诺福韦（TFV）和左炔诺孕酮（LNG）——两种预防HIV感染和意外怀孕的主要候选药物。我们研究了从同一根纤维（复合纤维）或堆叠或交织结构的不同纤维中递送这两种药物的复合材料中TFV和LNG组合的体外药物释放情况。对于堆叠复合材料，我们还研究了织物厚度对药物释放动力学的作用。我们还测量了单独给药和联合给药的细胞毒性和抗病毒活性。
在此，我们报告了具有可控微观结构和高载药量（高达20 wt%）的医用织物自由表面电纺的溶液和加工参数。我们观察到，高水溶性的TFV的体外释放受复合微观结构、织物厚度和药物含量的影响，而水不溶性的LNG不受影响。最后，我们表明载药纳米纤维无细胞毒性，并且TFV的抗病毒活性在电纺过程中以及与LNG联合时得以保留。
高载药量的电纺织物形成了多组分系统，受益于对纳米纤维微观结构的独立控制。我们的研究结果具有重要意义，因为它们将为复合电纺织物的设计和生产提供参考，用于联合递送物理化学性质各异的药物，这可能对多用途预防有用。
