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首页> 外文学位 >Fundamental mechanisms of drug delivery by jet injection: Basis for the development of a painless microject injector.
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Fundamental mechanisms of drug delivery by jet injection: Basis for the development of a painless microject injector.

机译：喷射注射给药的基本机理：无痛显微注射注射器的开发基础。

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Conventional needles are the primary method for the delivery of macromolecular drugs such as insulin and vaccines. However, patient compliance with needle injections is low, especially for chronic prescriptions. In addition, concern about the spread of disease around the world from needlestick injuries and the reuse of needles calls for the use of needle-free drug delivery methods.; Jet injection is a needle-free drug delivery method which employs a high-speed stream of fluid that impacts the skin and delivers drugs intradermally, subcutaneously, or intramuscularly often with quicker absorption and greater immune response from vaccines than by needle injections. Although jet injectors have been commercially used for vaccinations and insulin delivery since the 1940s, little had been known about the mechanism of jet injection or the parameters which control it. Occasional pain and variability associated with injections may have limited their widespread use. My research has focused on determining the overall mechanisms of drug delivery by jet injection in order to identify design parameters for a new generation of painless jet injectors.; The overall mechanism and controlling parameters of drug delivery were determined through experiments quantifying fluid penetration into human skin as a function of jet and material parameters, analyzing jet penetration into a model soft material, and measuring jet-impingement erosion of skin. Jet injection occurs by jet-induced erosion of skin followed by fluid dispersion into the skin. The quantity and depth of penetration are controlled by the jet velocity and nozzle diameter as well as the Young's modulus of the skin. The power of the jet, which described the effects of both jet velocity and nozzle diameter, was identified as a critical parameter for drug delivery due to its linear relationship with the quantity of delivery into skin. A predictive model of the erosion of the skin was developed that incorporates jet and skin properties as the first major step in mathematically predicting the depth and quantity of drug delivery by jet injection. As a result of these mechanistic studies guidelines were developed for a painless jet injector and implemented in a pulsed microjet injector for shallow intradermal delivery.
机译：传统的针头是用于输送大分子药物（例如胰岛素和疫苗）的主要方法。但是，患者对针头注射的依从性较低，尤其是对于慢性处方药。此外，由于担心针刺伤致世界范围内的疾病蔓延以及针头的重复使用，需要使用无针药物输送方法。喷射注射是一种无针药物输送方法，该方法采用高速流体流，该流体流会冲击皮肤，并且与针头注射相比，通常能更快地吸收疫苗并产生更大的免疫反应，从而在皮内，皮下或肌肉内输送药物。尽管自1940年代以来，喷射注射器已在商业上用于疫苗接种和胰岛素输送，但对于喷射注射的机理或控制它的参数知之甚少。与注射有关的偶发性疼痛和变异性可能限制了它们的广泛使用。我的研究集中在确定通过喷射注射进行药物输送的总体机制，以便确定新一代无痛喷射注射器的设计参数。药物输送的总体机制和控制参数是通过实验确定流体对人体皮肤的渗透力（作为射流和材料参数的函数），分析射流对模型软材料的渗透率以及测量射流对皮肤的侵蚀而确定的。喷射注射是通过喷射引起的皮肤侵蚀，然后流体分散到皮肤中而发生的。渗透的数量和深度由射流速度和喷嘴直径以及皮肤的杨氏模量控制。喷射力描述了喷射速度和喷嘴直径的影响，由于其与皮肤输送量的线性关系，被确定为药物输送的关键参数。开发了一种皮肤侵蚀的预测模型，该模型结合了喷射和皮肤特性，这是数学上预测通过喷射注射给药的深度和数量的第一步。这些机理研究的结果是，为无痛喷射注射器开发了指南，并在脉冲式微喷射注射器中实施了用于浅皮内输送的指南。

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