Transdermal delivery systems provide a convenient noninvasive approach for drug administration through the skin, and they have been widely developed for in-home health care. The stratum corneum of the skin surface limits drug penetration, but ultrasound (US)-stimulated microbubble (MB) cavitation can enhance skin permeability to promote transdermal drug penetration. However, the specific materials and complex fabrication of MBs influence the scope of application in transdermal delivery systems. Hence, we studied the mixture of citric acid and NaHCO₃ agents to generate shell-free CO₂-MBs by acid–base neutralization effect. The generation rate of CO₂-MBs was 36.3 ± 10 MBs/s and the mean size was 110 ± 14 μm under US sonication (3.1 MHz, 0.5 W/cm², 50% duty cycle, 1 min). The penetration of Evans blue and FITC-conjugated hyaluronic acid in rat abdominal skin by CO₂-MB cavitation improved 2.4 ± 0.3 and 2.1 ± 0.1 fold, respectively. The penetration depth of Evans blue (27.1 ± 5.1 μm) reached the epidermal layer, providing the potential for inducing transcutaneous immunization. Therefore, we proposed a simple and self-operating ultrasonic transdermal delivery system with CO₂-MB cavitation to improve drug penetration for in-home health care development.

中文翻译：

---

具有酸碱中和产生 CO2 微泡空化的超声透皮给药系统

透皮给药系统为通过皮肤给药提供了一种方便的非侵入性方法，并且它们已被广泛用于家庭保健。皮肤表面的角质层限制了药物的渗透，但超声 (US) 刺激的微泡 (MB) 空化可以增强皮肤渗透性以促进透皮药物渗透。然而，MBs 的特定材料和复杂制造影响了透皮给药系统的应用范围。因此，我们研究了柠檬酸和NaHCO ₃试剂的混合物通过酸碱中和作用产生无壳CO _{2 -MBs。}CO ₂ -MBs 的生成速率为 36.3 ± 10 MBs/s，在美国超声（3.1 MHz，0.5 W/cm ^{2 ）下的平均尺寸为 110 ± 14 μm}, 50% 占空比, 1 分钟)。伊文思蓝和 FITC 共轭透明质酸通过 CO ₂ -MB 空化作用在大鼠腹部皮肤中的渗透率分别提高了 2.4 ± 0.3 和 2.1 ± 0.1 倍。伊文思蓝的穿透深度（27.1 ± 5.1 μm）到达表皮层，为诱导经皮免疫提供了潜力。因此，我们提出了一种简单且自操作的具有 CO ₂ -MB 空化作用的超声透皮给药系统，以提高药物渗透性，从而促进家庭医疗保健的发展。