Advanced Systems for Transdermal Drug Delivery and Biofluid Extraction

Abstract

The global emergence of pandemics and ageing has accelerated the innovation of personalized medicine. Needle free injector (NFI) and microneedles (MN) are rising as next generation of transdermal administration tools for skin disease treatment, emphasizing minimal-invasive, user friendly and multi-functions, etc. For skin disease treatment, the pressing needs include controllable dosage, permeation depth of drug delivery and efficient extraction of body fluid. The recent advances have moved beyond the simple administration toward combing material science, physical field or bionics structures. We come up with hypothesis that the novel integration of physical field, responsive materials or bionics structures would facilitate the drug delivery and body fluid extraction.

The transdermal drug delivery for skin disease treatment by spring-based NFI is cost-effective but poor in pressure controllability, sometimes leaving unnecessary pain and ineffective absorption. In the first project, we studied jet permeation optimization by placing a layer of elastic membrane between the surface of the skin and the NFI outlet. The drug distribution within the injection target can be modulated by membrane thickness effectively. On the ex vivo model (porky skin), membrane-mediated NFI effectively reduced the injection depth (50% for aqueous solution and 40% for oil-based solution) and enhanced the horizontal diffusion (44% for aqueous solution and 8.1% for oil-based solution), compared with NFI only, leaving more drug in dermis. We conclude that elastic-membrane-assisted NFI offers a simple, speedy, and cost-effective strategy for intradermal drug delivery, potentially enhancing the efficacy for skin disease treatment.

Compared to NFI, microneedles have fixed permeation depth and drug dosage, enabled customized release profile on site. However, there is a pressing need to develop MN-based devices for on-demand release in space and dose when managing large skin lesion. In the second project, we have developed a wearable microneedle array for pressure-controlled drug release. The array interconnected by stretchable electrode array, on which the drug-loading MN units offered pressing-responsive iontophoresis on specific site, with 3-times-improved release rate and resolution of ~ 1.43 DPI. In the in-vivo blood glucose level (BGL) management test, the controllable release of insulin by MN array suppressed the post-prandial and general BGL for 12 hours. The MN array showed a concept for large-area delivery with the spatiotemporal controllability.

Besides, recent advances of MN-mediated extraction also promise wide prospect on personalized diagnosis of skin disease, or treatment that need extraction, such as exudate management of abscess. However, the current extraction based on porous/hollow MN is not suitable for large-amount extraction and bacterial collection. In the third project, we developed a bionics structural MN backing, namely horizontal-liquid-diode (HLDMN), to realize directional liquid transport, without external powering or vacuum pumping. Combing with absorption by weave layer, the flow rate for extraction was > 40 μl/s, and the maximum capacity for single use was > 600 μl. Furthermore, the in vitro and ex vivo test show that HLDMN also allowed for bacteria removal from mimic abscess model, and bacteria storage in weave layer, namely self-cleaning on backing. The CFU counting and histological staining show that HLDMN offered better anti-bacterial effect compared to commercial superabsorbent dressing, which supported unique possibility of treating highly exudating abscess as absorbent dressing.

Together, these research works focused on innovation of NFI and MN, to explore novel treatment methods with better efficiency of drug permeation, on-demand dose and body fluid extraction. The achievement from this dissertation would lay the groundwork for devices with multi-functions and personalized treatment.

Date of Award	18 Sept 2025
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Chenjie XU (Supervisor)