Hydrodynamically-driven drug release during interstitial flow through hollow fibers implanted near lymphatics.
Hydrodynamically-driven drug release during interstitial flow through hollow fibers implanted near lymphatics.
复制标题
间质流经淋巴管附近植入的中空纤维时，流体动力驱动的药物释放。
DOI：
10.1016/j.colsurfa.2016.08.052
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Labib,MohamedE
中科院分区：
文献类型：
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作者：
Dukhin,StanislavS;Labib,MohamedE
目前的给药装置（DDD）主要是利用扩散作为主要的输送过程。扩散驱动的过程只能实现低释放速率，因为扩散是一个缓慢的过程。这是最近在抑制淋巴转移和预防肢体和器官移植排斥方面取得成功的一个严重障碍。令人惊讶的是，人们忽略了在淋巴管附近植入特殊的DDD可以实现更有利的药物释放模式。当间质流体穿过适当设计的药物输送装置并允许此类流体流出时，可以实现这一机会。该设计基于载药中空纤维，其水动力渗透性远高于周围组织。后者被称为高水动力渗透中空纤维（HFHP）。间质流动容易穿透中空纤维膜及其管腔，其速度比邻近组织快。进入管腔的间质液体流在流出HFHP时几乎被药物饱和。这是由于药物粉末溶解在HFHP的管腔中，形成一条药物溶液带，穿过间质，最终进入淋巴管。这种流体动力驱动释放（HDR）可能超过伴随的扩散驱动释放（DDR）一个甚至两个数量级。双室介质的流体力学足以发展HDR理论，本文对此进行了详细介绍。当DDR对主导HDR的贡献很小时，需要两个隔室（中空纤维膜和邻近组织）的对流扩散理论进行精确量化。因此，建模对HDR至关重要，这将导致在物理化学流体动力学中建立一个新的分支。使用HFHP获得的释放率与用于药物递送的织物中中空纤维的数量成正比。基于这一贡献，现在有可能同时提供高释放率和长释放持续时间，从而克服了药物输送的基本限制。也许这一长期给药的突破在靶向淋巴系统和治疗癌症和癌症转移方面具有潜在的应用前景，而不会引起全身药物的严重副作用。
Current drug delivery devices (DDD) are mainly based on the use of diffusion as the main transport process. Diffusion-driven processes can only achieve low release rate because diffusion is a slow process. This represents a serious obstacle in the realization of recent successes in the suppression of lymphatic metastasis and in the prevention of limb and organ transplant rejection. Surprisingly, it was overlooked that there is a more favorable drug release mode which can be achieved when a special DDD is implanted near lymphatics. This opportunity can be realized when the interstitial fluid flow penetrates a drug delivery device of proper design and allows such fluid to flow out of it. This design is based on hollow fibers loaded with drug and whose hydrodynamic permeability is much higher than that of the surrounding tissue. The latter is referred to as hollow fiber of high hydrodynamic permeability (HFHP). The interstitial flow easily penetrates the hollow fiber membrane as well as its lumen with a higher velocity than that in the adjacent tissue. The interstitial liquid stream entering the lumen becomes almost saturated with drug as it flows out of the HFHP. This is due to the drug powder dissolution in the lumens of HFHP which forms a strip of drug solution that crosses the interstitium and finally enters the lymphatics. This hydrodynamically-driven release (HDR) may exceed the concomitant diffusion-driven release (DDR) by one or even two orders of magnitude. The hydrodynamics of the two-compartment media is sufficient for developing the HDR theory which is detailed in this paper. Convective diffusion theory for two compartments (membrane of hollow fiber and adjacent tissue) is required for exact quantification when a small contribution of DDR to predominating HDR is present. Hence, modeling is important for HDR which would lead to establishing a new branch in physico-chemical hydrodynamics. The release rate achieved with the use of HFHP increases proportional to the number of hollow fibers in the fabric employed in drug delivery. Based on this contribution, it is now possible to simultaneously provide high release rates and long release durations, thus overcoming a fundamental limitation in drug delivery. Perhaps this breakthrough in long-term drug delivery has potential applications in targeting lymphatics and in treating cancer and cancer metastasis without causing the serious side effects of systemic drugs.