Predicting the tissue depth for remote triggering of drug delivery systems.
Predicting the tissue depth for remote triggering of drug delivery systems.
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DOI：
10.1016/j.jconrel.2018.07.033
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发表时间：
2018-09-28
期刊：
影响因子：
--
通讯作者：
Kohane DS
中科院分区：
文献类型：
--
作者：
Rwei AY;Wang B;Ji T;Kohane DS
可外用给药系统在根据患者的需要灵活控制治疗的时间、持续时间和强度，同时减少副作用和提高治疗效果方面具有很好的潜力。然而，将这样的系统转化为临床实践的限制是难以预测这样的系统可以在体内安全使用的组织深度（例如，可以在靶部位用临床安全的能量剂量激活）。需要一种有效的方法来评价外部可降解药物递送系统的临床潜力。在这里，我们有一种方法和途径来预测组织深度，在该深度处，药物递送系统可以通过外部能量源在体内安全地触发。我们使用体外和离体实验结合数学模型来开发一种方法来预测不同组织深度的活化药物释放，然后在体内进行验证。我们构建了这些模型的脂质体药物输送系统触发的两个最常用的研究外部刺激：超声波和近红外光。我们在两种常见的组织类型中开发了这种方法：肌肉和脂肪。我们的方法确定了组织中药物递送系统激活的两个重要参数：1）激活能穿透组织的能力，2）系统对激活源的敏感性。该方法通过与大鼠体内触发坐骨神经阻滞的相关性进行了验证，表明该方法提供了对不同组织深度的激活释放的准确估计。
Externally triggerable drug delivery systems have promising potential in providing flexible control of the timing, duration, and intensity of treatment according to patient’s needs, while reducing side effects and increasing therapeutic efficacy. However, a limitation to translating such systems into clinical practice is the difficulty to predict the tissue depth at which such systems could be safely used in vivo (e.g. activatable at the target site with a clinically-safe energy dosage). An effective method is needed to evaluate the clinical potential of externally triggerable drug delivery systems. Here we have a method and approach to predicting the tissue depth at which a drug delivery system can be safely triggered in vivo by an external energy source. We used in vitro and ex vivo experiments combined with a mathematical model to develop a method to predict activated drug release at different tissue depths, which was then validated in vivo. We constructed these models for liposomal drug delivery systems triggered by two of the most commonly studied external stimuli: ultrasound and near infrared light. We developed the approach in two prevalent tissue types: muscle and fat. Our method identified two important parameters in the activation of drug delivery systems in tissue: 1) the ability of the activation energy to penetrate tissue, 2) the sensitivity of the system to the activation source. The method was validated by correlation with triggered sciatic nerve block in the rat in vivo, demonstrating that this approach provided an accurate estimate of activated release at different tissue depths.
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影响因子：
28.1
作者：
Rwei AY;Paris JL;Wang B;Wang W;Axon CD;Vallet-Regí M;Langer R;Kohane DS
通讯作者：
Kohane DS
影响因子：
15
作者：
Huschka, Ryan;Zuloaga, Jorge;Knight, Mark W.;Brown, Lisa V.;Nordlander, Peter;Halas, Naomi J.
通讯作者：
Halas, Naomi J.
影响因子：
3.4
作者：
Olbrich, K;Rawicz, W;Evans, E
通讯作者：
Evans, E
影响因子：
2.2
作者：
DerSimonian, Rebecca;Kacker, Raghu
通讯作者：
Kacker, Raghu
影响因子：
16.6
作者：
Carter, Kevin A.;Shao, Shuai;Hoopes, Matthew I.;Luo, Dandan;Ahsan, Bilal;Grigoryants, Vladimir M.;Song, Wentao;Huang, Haoyuan;Zhang, Guojian;Pandey, Ravindra K.;Geng, Jumin;Pfeifer, Blaine A.;Scholes, Charles P.;Ortega, Joaquin;Karttunen, Mikko;Lovell, Jonathan F.
通讯作者：
Lovell, Jonathan F.