The majority of infectious diseases enter the body through mucosal membranes that line the ocular, nasal, oral, vaginal and rectal surfaces. As infections can be effectively prevented by instigating a local immune response in the immunocyte-rich regions of the mucosa, an efficacious route of vaccine administration is to directly target their delivery to these surfaces. It is nevertheless challenging to provide sufficient driving force to penetrate both the mucus lining as well as the epithelial barrier of the mucosal surfaces, which are designed to effectively keep foreign entities out, but not excessively such that the therapeutic agent penetrates deeper into the vascularised submucosal regions where they are mostly taken up by the systemic circulation, thus resulting in a far weaker immune response. In this work, we demonstrate the possibility of controllably localising and hence maximising the delivery of both small and large molecule model therapeutic agents in the mucosa of a porcine buccal model using high frequency acoustics. Unlike their low (kHz order) frequency bulk ultrasonic counterpart, these high frequency (>10 MHz) surface waves do not generate cavitation, which leads to large molecular penetration depths beyond the 100 μm order thick mucosal layer, and which has been known to cause considerable cellular/tissue damage and hence scarring. Through system parameters such as the acoustic irradiation frequency, power and exposure duration, we show that it is possible to tune the penetration depth such that over 95% of the delivered drug are localised within the mucosal layer, whilst preserving their structural integrity.

中文翻译：

---

药物通过组织的高频声透性，用于局部粘膜递送

大多数传染病通过粘膜进入人体，该粘膜位于眼，鼻，口腔，阴道和直肠表面。由于可以通过在粘膜的富含免疫细胞的区域内激发局部免疫反应来有效地预防感染，因此疫苗接种的有效途径是直接将其递送至这些表面。然而，提供足够的驱动力以穿透粘膜内衬和粘膜表面的上皮屏障是挑战性的，这被设计为有效地将异物拒之门外，但又不过分地使得治疗剂更深地渗透到血管化的粘膜下层它们大部分被全身循环吸收的区域，因此导致免疫反应弱得多。在这项工作中，我们证明了使用高频声学技术可控制地定位并因此最大化小分子模型治疗剂和大分子模型治疗剂在猪口腔模型粘膜中的传递的可能性。与它们的低频（kHz级）整体超声对应物不同，这些高频（> 10 MHz）表面波不会产生空化现象，这会导致超过100μm厚的粘膜层的大分子穿透深度，并且已知会引起相当大的细胞/组织损伤，从而形成疤痕。通过系统参数（例如声辐射频率，功率和暴露持续时间），我们表明可以调节穿透深度，以使超过95％的所递送药物位于粘膜层内，同时保留其结构完整性。