Tobos Carmen I, Woodrow Kim A
Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA.
Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, USA.
Acta Biomater. 2025 Jun 15;200:115-131. doi: 10.1016/j.actbio.2025.05.025. Epub 2025 May 9.
Dissolving microneedles deliver many classes of nucleic acids, overcoming susceptibility to enzymatic cleavage and poor intracellular delivery. Understanding the impact of microneedle formulation on nucleic acid therapeutic efficacy is critical for clinical translation. Here, we performed a systematic search to identify preclinical dissolving microneedle studies that deliver nucleic acid therapeutics including aptamers, DNA enzymes, mRNA, miRNA, plasmid DNA, recombinant viral vectors, and siRNA. This review quantitatively synthesizes preclinical data to identify correlations between microneedle form and function. Factors such as polymer molecular weight and incorporation of a nucleic acid carrier strongly influence mechanical and biological properties, while other design parameters allow for more flexibility. Altogether, 83 % of studies show equivalent or superior efficacy to existing nucleic acid administration routes including topical, subcutaneous, and intramuscular administration. Data especially supports the use of dissolving microneedles for viral and cancer vaccine applications, with a growing body of work exploring their utility for gene silencing. Nonetheless, several knowledge gaps remain. Emerging nucleic acid carrier chemistries that retain efficacy with improved toxicity profiles will define the next generation of formulations. Plasmid DNA and viral vectors show excellent long-term stability in dissolving microneedles, but further characterization is needed for long RNA transcripts. Finally, future work could explore the potential for non-dermal administration routes, as well as co-delivery of nucleic acids with small molecules to leverage synergistic effects. STATEMENT OF SIGNIFICANCE: This review comprehensively, critically, and quantitatively synthesizes preclinical dissolving microneedles for nucleic acid delivery. This approach identifies empirically supported correlations between microneedle form and function, highlighting evidence-based best practices and remaining challenges. The form-function relationships identified in this review will be valuable to those within the immediate microneedle field, as well as more broadly to audiences interested in nucleic acid therapeutics, drug delivery systems, microfabrication, and delivery strategies for low resource settings.
溶蚀性微针可递送多种类型的核酸，克服了核酸易被酶切以及细胞内递送效果不佳的问题。了解微针制剂对核酸治疗效果的影响对于临床转化至关重要。在此，我们进行了一项系统检索，以识别递送核酸治疗药物（包括适体、脱氧核酶、信使核糖核酸、微小核糖核酸、质粒脱氧核糖核酸、重组病毒载体和小干扰核糖核酸）的临床前溶蚀性微针研究。本综述对临床前数据进行了定量综合分析，以确定微针形式与功能之间的相关性。诸如聚合物分子量和核酸载体的掺入等因素会强烈影响机械性能和生物学性能，而其他设计参数则具有更大的灵活性。总体而言，83%的研究表明，其疗效等同于或优于包括局部、皮下和肌肉注射在内的现有核酸给药途径。数据特别支持将溶蚀性微针用于病毒和癌症疫苗应用，并且越来越多的研究正在探索其在基因沉默方面的效用。尽管如此，仍存在一些知识空白。保留疗效并改善毒性特征的新型核酸载体化学将定义下一代制剂。质粒脱氧核糖核酸和病毒载体在溶蚀性微针中显示出出色的长期稳定性，但对于长链核糖核酸转录本还需要进一步表征。最后，未来的工作可以探索非皮肤给药途径的潜力，以及核酸与小分子的联合递送以发挥协同效应。重要性声明：本综述全面、批判性地且定量地综合分析了用于核酸递送的临床前溶蚀性微针。这种方法确定了微针形式与功能之间基于经验的相关性，突出了基于证据的最佳实践和 remaining challenges。本综述中确定的形式 - 功能关系对于直接从事微针领域研究的人员以及更广泛地对核酸治疗、药物递送系统、微制造和低资源环境下的递送策略感兴趣的受众都将具有价值。 （注：原文中“remaining challenges”未翻译完整，可能是文档录入问题，根据语境推测应是指剩余的挑战，但按要求未添加额外解释）
