Ultrasonic Permeation of Stimuli-Responsive Microgels through Porous Media as a Model Process for Drug Transfer

无针给药(NFDD)系统将特定数量的药物驱动到给药部位，通过可重复使用的选项绕过皮下注射针。实现成功的药物输送取决于使液体喷射并加速它的能力，同时不会对皮肤或药物分子的完整性造成损害。提出的研究的主要目标是利用高频超声波(MHz级)从微凝胶水溶液中形成薄液体射流，并渗透到模拟的多孔组织中。聚(N-异丙基丙烯酰胺)(PNIPAM)微凝胶具有温度响应性，在32℃时发生体积相变，将被用作药物载体的模型体系。一方面，形成含有膨胀的PNIPAM微凝胶的稳定的液体射流，另一方面，它穿透多孔组织的能力，是拟议研究的最重要目标。第二个目标是引入和研究高频声波作为PNIPAM微凝胶的一种新的刺激。初步实验表明，在足够低的激励幅值下，液-气界面不会形成射流。因此，溶液有足够的时间吸收足够的能量来打破氢键，PNIPAM微凝胶由于吸收声能而不是热能而经历了体积相变。这为利用超声驱动形成射流开辟了一个新的研究方向。

Needle-free drug delivery (NFDD) systems drive a specific amount of a drug into the site of delivery, bypassing the hypodermic needle with a reusable option. Achieving a successful drug delivery depends on the ability to make the liquid jet and accelerate it while no harm is done to the skin or the integrity of drug molecules. The primary goal of the proposed research is to utilize high-frequency ultrasonic (MHz-order) waves to form a thin liquid jet from microgel aqueous solutions and permeate through a simulated porous tissue. Poly(N-isopropylacrylamide) (PNIPAM) microgels, which are thermo-responsive and undergo a volume phase transition at 32 °C, will be used as the model system for drug carriers. Formation of a stable liquid jet that contains swollen PNIPAM microgels on the one hand and its ability to penetrate through the porous tissue, on the other hand, are the most important objectives of the proposed research. A secondary goal is to introduce and investigate the high-frequency acoustic waves as a novel stimulus for PNIPAM microgels. It was shown in preliminary experiments that upon low enough excitation amplitude, the liquid-air interface does not experience the jet formation. Hence, the solution has sufficient time to absorb adequate energy for breaking the hydrogen bonds and PNIPAM microgels undergo a volume phase transition due to the absorption of acoustic energy instead of thermal energy. This opens up a new research direction in contrast to jet formation using ultrasonic actuation.