Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Conventional administration methods have problems including low bioavailability, complex operation process, and discomfort of patients with fear of needles. Transdermal delivery can avoid these problems, whereas most drugs are difficult to directly penetrate the skin cuticle and reach the diseased site. Microneedling is an emerging method of local drug delivery, enabling the drug penetration through the stratum corneum of the skin in a minimally invasive manner and delivering the drug directly to the diseased site, thereby improving the treatment effect. Stimuli-responsive microneedles have attracted much attention because of the spatiotemporal controllability, high drug delivery efficiency, and mild potential side effects. This review introduced the commonly used materials and various types of stimuli-responsive microneedles and the drug release mechanisms. In addition, this paper expounded the biomedical applications of stimuli-responsive microneedles as drug delivery systems in response to different stimuli and discusses the challenges and potential solutions for stimuli-responsive microneedles.
Needles ; Drug Delivery Systems/instrumentation* ; Microinjections/instrumentation* ; Humans ; Administration, Cutaneous

It is very important to disrupt the stratum corneum structure and to create pathways allowing transport of macromolecules, as the traditional transdermal drug delivery has been severely limited by the skin barrier. With the development of the Micro Electro-Mechanical System (MEMS), it becomes possible for microneedles array to strengthen the transdermal drug delivery. In addition to the increase of the skin permeability, it can also be used to deliver drugs into skin, such as insulin and vaccine, providing a new direction for drug delivery systems. In this paper, we review the development and applications in transdermal drug delivery of microneedles' array. The commercial prospects and recommendations for the future research work are also represented.
Administration, Cutaneous ; Drug Delivery Systems ; instrumentation ; Equipment Design ; Micro-Electrical-Mechanical Systems ; Microinjections ; Needles

Microneedles array based on micro electro-mechanical system (MEMS) technology is one of important applications in biomedicine and brings a new means in biomedicine field. The prospect for the development of microneedles technology in precision drug injection, clinical monitoring and biochemistry test is and save broad. This paper describes three important applications of MEMS microneedles array in biomedicine field: biomedicine microneedles electrode, transdermal delivery of drugs and fluid extraction, and then summarizes their application elements and recent development. It explains the characteristics of microneedles, which provide painless, effective and save biomedical method in accordance with human requirements. In addition, a series of the fabrication technology of microneedles array is discussed.
Drug Delivery Systems ; instrumentation ; Equipment Design ; Humans ; Microelectrodes ; Microinjections ; instrumentation ; Miniaturization ; Nanotechnology ; Needles