Schramm Joy, Mitragotri Samir
Department of Chemical Engineering, University of California, Santa Barbara 93106, USA.
Pharm Res. 2002 Nov;19(11):1673-9. doi: 10.1023/a:1020753329492.
Pressure-driven jets have been used for intradermal delivery of a variety of drugs. Despite their introduction into clinical medicine, variability and occasional bruising have limited their widespread acceptance. Although numerous clinical studies of jet injectors have been reported in the literature, surprisingly little is known about the mechanisms of jet penetration into the skin. In this article, we report results of our studies aimed at determining the dependence of drug delivery on jet velocity and diameter. These studies were performed using two experimental models, porcine skin and human skin. Our rationale for using two models was to explore the possibility of using porcine skin as a model for human skin.
Dermal penetration of jets possessing a range of diameters from 76 microm to 559 microm and a range of velocities from 80 m/s to 190 m/s was studied into human and porcine skin. Penetration was quantified using radiolabeled mannitol. Pressure and velocity of the jets were measured using a calibrated pressure transducer and high-speed photography.
Penetration of the jet into the skin was determined by two main parameters, jet diameter and average jet velocity. Substantial variation in jet penetration into porcine skin was observed for skin pieces obtained from different anatomic locations. For porcine skin, a parabolic dependence of jet delivery on velocity and diameter was observed. The threshold velocity is suggested to be between 80 and 100 m/s for a jet diameter of 152 microm. Above the threshold velocity, the delivery increased for velocities up to 150 m/s, after which delivery decreased with increasing velocity. At a constant velocity of 150 m/s, jet delivery exhibited a maximum at a diameter of 152 microm. Results obtained with human skin were qualitatively similar but quantitatively different. The threshold velocity for jet penetration into human skin was comparable with that in porcine skin; however, the maxima observed in jet delivery into porcine skin with respect to jet velocity was not apparent for human skin over the range of velocities explored.
These studies offer a quantitative analysis of jet penetration into the skin.
压力驱动射流已被用于多种药物的皮内给药。尽管它们已被引入临床医学，但变异性和偶尔出现的瘀伤限制了它们的广泛应用。虽然文献中已报道了大量关于射流注射器的临床研究，但令人惊讶的是，对于射流穿透皮肤的机制知之甚少。在本文中，我们报告了旨在确定药物递送对射流速度和直径依赖性的研究结果。这些研究使用了两种实验模型，猪皮和人皮。我们使用两种模型的理由是探索将猪皮用作人皮模型的可能性。
研究了直径范围为76微米至559微米、速度范围为80米/秒至190米/秒的射流对人和猪皮肤的真皮穿透情况。使用放射性标记的甘露醇对穿透情况进行定量。使用校准的压力传感器和高速摄影测量射流的压力和速度。
射流对皮肤的穿透由两个主要参数决定，即射流直径和平均射流速度。对于从不同解剖位置获得的皮肤样本，观察到射流对猪皮肤的穿透存在显著差异。对于猪皮，观察到射流递送对速度和直径呈抛物线依赖性。对于直径为152微米的射流，阈值速度建议在80至100米/秒之间。高于阈值速度时，递送量随速度增加至150米/秒而增加，之后递送量随速度增加而减少。在150米/秒的恒定速度下，射流递送在直径为152微米时达到最大值。用人皮获得的结果在定性上相似但在定量上不同。射流穿透人皮的阈值速度与猪皮中的相当；然而，在探索的速度范围内，对于人皮而言，射流递送相对于射流速度在猪皮中观察到的最大值并不明显。
这些研究提供了对射流穿透皮肤的定量分析。
