微针技术在经皮给药系统中应用的研究进展

微针在研发初期主要用于药物的输送,可以克服传统经皮给药的局限性,是继口服和注射之后的一种给药新途径。介绍了微针的类型及其释药机制,阐述了固体、涂层、空心、溶解、水凝胶5种类型微针的给药方式的优缺点及其在经皮给药领域中应用的最新研究进展。说明了不同的微针类型适用于不同性质的药物输送,当前先进的微针经皮给药系统可以显著提高药物经皮的渗透量,达到良好的治疗效果。此外,还对微针在当前发展中可能存在的问题进行了探讨,并对其在未来的发展前景进行了展望。     

可溶性微针在经皮给药系统中应用的研究进展

对微针在经皮给药系统中的优势进行了简单阐述,重点介绍了可溶性微针。可溶性微针由生物相容性和水溶性的基质材料制成,具有可生物降解、载药量大、不产生针尖废物等独特优势。从可溶性微针常用的基质种类和制备方法阐述了可溶性微针对药物经皮渗透和吸收的影响。对国内外研究中可溶性微针递送疫苗、降糖药、基因、麻醉剂、抗肿瘤药物和其他应用进行了介绍。总结出可溶性微针经皮给药系统可显著提高药物的经皮渗透量,能够安全、稳定地输送药物并达到良好的治疗效果。最后,对可溶性微针现研究阶段存在的问题进行了分析,并展望了未来发展的方向。     

用于药物释放系统的柔性微针研制

提出了一种基于MEMS技术在柔性基底上制造微针的工艺技术,这是一种高效、安全和无痛的全新给药方式-微针阵列.该微针阵列能够适用于平面或非平面物体表面,对大分子药剂、蛋白质或者疫苗合成药剂也能够使用.     

新型MEMS微针设计及其力学性能

描述了三种新型MEMS微针的结构设计及制备方法.针对微针的实际使用要求,对微针的固体力学性质及微通道内液体的流动情况进行了理论分析和数值模拟.结果表明,所设计的三种微针的强度可以保证安全地进行皮肤注射,且适于进行药剂的微量传输.     

新型MEMS微针设计及其力学性能

描述了三种新型MEMS微针的结构设计及制备方法.针对微针的实际使用要求,对微针的固体力学性质及微通道内液体的流动情况进行了理论分析和数值模拟.结果表明,所设计的三种微针的强度可以保证安全地进行皮肤注射,且适于进行药剂的微量传输.     

基于MEMS微针技术的研究现状与展望

基于MEMS的微针技术研究是当前药物传输领域中的热点。随着微细加工技术的发展,微针技术及其应用得到了快速发展,除了向生物体内传输药物和向细胞内传输DNA外,还可以用来监测和反馈药物对生物体的影响及外源DNA在受体内的表达形式,同时在植入式器械方面也有所发展。本文综述了基于MEMS微针技术及应用的发展状况。     

一种聚合物实心微针的制作方法

为实现制作微针加工工艺简单、加工周期短及成本低的目的,提出了一种制作聚合物微针的新方法,这种聚合物微针的制作过程主要包括三个部分:微针原始模具的制作、聚合物微针模具的制作和浇铸工艺复制微针。通过KOH腐蚀液刻蚀晶面为{100}的Si片和紫外线对准光刻SU8胶得到由Si-SU8胶构成的原始模具,再在该模具上注入聚二甲基硅氧烷(PDMS)进行转模,固化脱模后在PDMS微针二级模具表面溅射一层Cu/Cr金属薄膜,然后再注入PDMS,得到最终的聚合物微针模具,对该模具进行浇铸工艺,便可批量制作微针。通过浇注PDMS获得微针初始结构,使针尖和针体合为一体,提高了脱模的可靠性;通过改变设计,能得到不同截面尺寸和长度的微针,因此这种方法具有很高的灵活性。     

MEMS微针制备及其应用研究的进展

微电子机械系统(MEMS)微针是目前的一个研究热点,在生物医学上有着广泛的应用.该文介绍了一些新的微针制备方法,对它们的优缺点进行了分析.另外,综述了微针应用研究的最新进展,指出了其面临的挑战和未来的发展趋势.     

SU-8微针执行器的研究

设计和采用MEMS工艺技术制作了一种由电磁驱动的微量取样执行器。执行器的结构包括微针、通道、反应室、电极以及永磁微阵列等。通过外部磁场可以实现双向线性驱动。本文主要介绍了利用SU 8光刻胶材料 ,采用多级曝光实现 3D结构的工艺技术 ,研制出了微针执行器的雏形器件。微针的尺寸为 6 0 0 μm× 80 0 μm× 4 0 μm ,微针孔径截面为 2 0 μm× 2 0 μm ,并给出了SEM分析的研究结果     

用于增强药物和疫苗经皮给送的微针技术

作为一种微米尺度的类似针状器件,微针可以克服传统经皮给药(TDD)的局限,在皮肤上无痛、无出血地产生微米量级的孔洞,提高药物尤其是大分子化合物的经皮递送效果。介绍了TDD用微针根据不同给药方法进行的分类和相应的微制造方法。给出了四种微针的给药方案和一般使用方法,说明了各种微针给药方案的优缺点及一些改进措施。比较全面地阐述了微针在治疗、监测、诊断、美容等方面的应用及研究进展。微针在TDD技术的发展过程中起到了重要的促进作用,其未来的发展将在微加工技术进步的支撑下,通过临床医学实践,进一步改善人类健康、提高生活品质。     

Limpet Tooth-Inspired Painless Microneedles Fabricated by Magnetic Field-Assisted 3D Printing

Microneedle arrays show many advantages in drug delivery applications due to their convenience and reduced risk of infection. Compared to other microscale manufacturing methods, 3D printing easily overcomes challenges in the fabrication of microneedles with complex geometric shapes and multifunctional performance. However, due to material characteristics and limitations on printing capability, there are still bottlenecks to overcome for 3D printed microneedles to achieve the mechanical performance needed for various clinical applications. The hierarchical structures in limpet teeth, which are extraordinarily strong, result from aligned fibers of mineralized tissue and protein-based polymer reinforced frameworks. These structures provide design inspiration for mechanically reinforced biomedical microneedles. Here, a bioinspired microneedle array is fabricated using magnetic field-assisted 3D printing (MF-3DP). Micro-bundles of aligned iron oxide nanoparticles (aIOs) are encapsulated by polymer matrix during the printing process. A bioinspired 3D-printed painless microneedle array is fabricated, and suitability of this microneedle patch for drug delivery during long-term wear is demonstrated. The results reported here provide insights into how the geometrical morphology of microneedles can be optimized for the painless drug delivery in clinical trials.     

Composite Dissolving Microneedles for Coordinated Control of Antigen and Adjuvant Delivery Kinetics in Transcutaneous Vaccination

Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, a microneedle materials platform is demonstrated for rapid implantation of controlled‐release polymer depots into the cutaneous tissue. Arrays of microneedles composed of drug‐loaded poly(lactide‐co‐glycolide) (PLGA) microparticles or solid PLGA tips are prepared with a supporting and rapidly water‐soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforate the stratum corneum and epidermis. Penetration of the outer skin layers is followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which are retained following patch removal. These polymer depots remain in the skin for weeks following application and sustain the release of encapsulated cargos for systemic delivery. To show the utility of this approach the ability of these composite microneedle arrays to deliver a subunit vaccine formulation is demonstrated. In comparison to traditional needle‐based vaccination, microneedle delivery gives improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.     

Hydrogel‐Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery

Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch‐type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.     

A Patch of Detachable Hybrid Microneedle Depot for Localized Delivery of Mesenchymal Stem Cells in Regeneration Therapy

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, a detachable hybrid microneedle depot (d‐HMND) for cell delivery is presented. The system consists of an array of microneedles with an outer poly(lactic‐co‐glycolic) acid shell and an internal gelatin methacryloyl (GelMA)‐MSC mixture (GMM). The GMM is characterized and optimized for cell viability and mechanical strength of the d‐HMND required to penetrate mouse skin tissue is also determined. MSC viability and function within the d‐HMND is characterized in vitro and the regenerative efficacy of the d‐HMND is demonstrated in vivo using a mouse skin wound model.     

Efficient Drug Delivery into Skin Using a Biphasic Dissolvable Microneedle Patch with Water-Insoluble Backing

Dissolvable microneedle patches (MNPs) enable simplified delivery of therapeutics via the skin. However, most dissolvable MNPs do not deliver their full drug loading to the skin because only some of the drug is localized in the microneedles (MNs), and the rest remains adhered to the patch backing after removal from the skin. In this work, biphasic dissolvable MNPs are developed by mounting water-soluble MNs on a water-insoluble backing layer. These MNPs enable the drug to be contained in the MNs without migrating into the patch backing due to the inability of the drugs to partition into the hydrophobic backing materials during MNP fabrication. In addition, the insoluble backing is poorly wetted upon MN dissolution in the skin, which significantly reduces drug residue on the MNP backing surface after application. These effects enable a drug delivery efficiency of >90% from the MNPs into the skin 5 min after application. This study shows that the biphasic dissolvable MNPs can facilitate efficient drug delivery to the skin, which can improve the accuracy of drug dosing and reduce drug wastage.     

SU-8光刻胶去胶工艺研究

SU-8光刻胶因具有良好的机械耐久性、聚合物水密性、介电性能、生物兼容性和抗化学腐蚀性而被广泛用于MEMS器件、生物医学和芯片封装等领域。现有制作工艺中,在不损伤器件的同时完全去除和剥离SU-8光刻胶仍是一个难题。文章研究了一种基于O₂/CF₄等离子刻蚀配合湿法刻蚀的去除方法,实现了SU-8光刻胶在硅基底、非晶无机非金属材料、电镀金属等材料上的有效去除。