Sanjanwala Dhruv, Shinde Aditya, Patravale Vandana
Department of Pharmaceutical Sciences, College of Pharmacy, 428 Church Street, University of Michigan, Ann Arbor, MI 48109, United States; Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019 Maharashtra, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019 Maharashtra, India.
Int J Pharm. 2025 Sep 15;682:125874. doi: 10.1016/j.ijpharm.2025.125874. Epub 2025 Jun 20.
Microneedles (MNs) are minimally invasive devices that facilitate transdermal delivery by creating micropores in the stratum corneum, the skin's outermost barrier. This property renders them particularly suitable for the delivery of biologics - large, structurally complex, and often unstable therapeutic agents such as proteins, peptides, nucleic acids, vaccines, and live cells or microorganisms. MNs offer a painless, self-administrable, and user-friendly alternative to conventional parenteral routes that often require trained personnel, generate hazardous waste, and result in low patient compliance. Since their first description in the 1990s, a wide variety of MN systems have been developed including solid, hollow, coated, dissolving, and hydrogel-forming, each with distinct fabrication and formulation requirements. This review provides a detailed and comparative discussion on formulation strategies tailored for the efficient delivery of different classes of biologics using MNs, with emphasis on the physicochemical and biological interactions at the skin interface. Special attention is given to sterilization, an often-overlooked yet regulatory-critical aspect, highlighting its importance for product safety, bioburden control, and biologic stability. Both terminal sterilization methods and aseptic manufacturing approaches are reviewed along with emerging alternatives such as self-sterilizing MNs. The review also provides a comprehensive overview of biologic-loaded MNs currently undergoing clinical evaluation. While previous reviews have focused on materials or fabrication aspects, this article presents a formulation-centric analysis, integrating physicochemical considerations, delivery challenges, and clinical translation pathways. The goal is to provide formulation scientists and translational researchers with a practical guide to MN-enabled biologic delivery systems, from bench to bedside.
微针(MNs)是一种微创装置,通过在皮肤最外层屏障角质层中制造微孔来促进经皮给药。这一特性使其特别适合递送生物制剂——如蛋白质、肽、核酸、疫苗以及活细胞或微生物等大型、结构复杂且通常不稳定的治疗剂。与传统的肠胃外给药途径相比,微针提供了一种无痛、可自行给药且用户友好的替代方法,传统途径通常需要专业人员操作,会产生有害废物,且患者依从性较低。自20世纪90年代首次被描述以来,已开发出多种微针系统,包括实心、空心、涂层、可溶解和形成水凝胶的微针,每种微针都有独特的制造和配方要求。本综述详细且比较性地讨论了为使用微针高效递送不同类型生物制剂量身定制的配方策略,重点关注皮肤界面处的物理化学和生物相互作用。特别关注灭菌这一常被忽视但在监管方面至关重要的方面,强调其对产品安全、生物负载控制和生物制剂稳定性的重要性。综述了终端灭菌方法和无菌制造方法以及新兴的替代方法,如自灭菌微针。该综述还全面概述了目前正在进行临床评估的负载生物制剂的微针。虽然之前的综述侧重于材料或制造方面,但本文提出了以配方为中心的分析,整合了物理化学因素、递送挑战和临床转化途径。目标是为配方科学家和转化研究人员提供一份从实验室到床边的关于基于微针的生物制剂递送系统的实用指南。