{"title":"Development and Evaluation of Dual Microneedle Array Patch for Sequential Intradermal Delivery of Adjuvant and Antigen.","authors":"Ye-Lim Lee, Hye-Ran Cha, Da-Eun Lee, Minwoo Ryu, Hyeon Woo Chung, Sunghoon Park, Jung-Ah Choi, Seung-Ki Baek, Jae Myun Lee, Jung-Hwan Park","doi":"10.1007/s11095-025-03914-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Adjuvants are critical for enhancing immune responses to recombinant protein-based vaccines, which typically exhibit weak immunogenicity. Microneedle array patches (MAPs) offer a promising method for intradermal delivery, but conventional Co-Delivery MAPs (containing antigen and adjuvant together) have limited loading capacity and potential undesirable interactions. Adjuvants may also trigger adverse reactions in sensitive populations. This study aimed to develop a Dual-Delivery MAP system that enables separate and sequential administration of antigens and adjuvants, addressing these limitations and supporting personalized vaccination strategies.</p><p><strong>Methods: </strong>The Dual-Delivery MAP was developed using a coated MAP for ovalbumin (OVA) and a dissolving MAP for the CTA1 adjuvant. Patches were sequentially applied to the same skin site. Delivery efficiency, intradermal distribution, and immunogenicity were evaluated and compared to a conventional Co-Delivery MAP and an intramuscular (IM) injection group (OVA and CTA1 in solution). OVA- and CTA1-specific IgG titers were measured to assess immune responses.</p><p><strong>Results: </strong>Both Dual-Delivery and Co-Delivery MAPs demonstrated similar delivery efficiency (~ 70%). However, the Dual-Delivery MAP elicited significantly higher IgG titers against CTA1 and OVA compared to the Co-Delivery MAP, likely due to enhanced adjuvant functionality. The Dual-Delivery MAP induced immune responses comparable to IM injection, indicating that sequential delivery preserves adjuvant activity and enhances immunogenicity.</p><p><strong>Conclusions: </strong>The Dual-Delivery MAP represents a novel, modular approach for skin-targeted vaccination. By separating antigen and adjuvant into distinct patches, it improves stability, maintains adjuvant efficacy, and enables personalized vaccine administration, offering a promising strategy for effective and safe vaccination.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"1559-1572"},"PeriodicalIF":4.3000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11095-025-03914-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/4 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Adjuvants are critical for enhancing immune responses to recombinant protein-based vaccines, which typically exhibit weak immunogenicity. Microneedle array patches (MAPs) offer a promising method for intradermal delivery, but conventional Co-Delivery MAPs (containing antigen and adjuvant together) have limited loading capacity and potential undesirable interactions. Adjuvants may also trigger adverse reactions in sensitive populations. This study aimed to develop a Dual-Delivery MAP system that enables separate and sequential administration of antigens and adjuvants, addressing these limitations and supporting personalized vaccination strategies.
Methods: The Dual-Delivery MAP was developed using a coated MAP for ovalbumin (OVA) and a dissolving MAP for the CTA1 adjuvant. Patches were sequentially applied to the same skin site. Delivery efficiency, intradermal distribution, and immunogenicity were evaluated and compared to a conventional Co-Delivery MAP and an intramuscular (IM) injection group (OVA and CTA1 in solution). OVA- and CTA1-specific IgG titers were measured to assess immune responses.
Results: Both Dual-Delivery and Co-Delivery MAPs demonstrated similar delivery efficiency (~ 70%). However, the Dual-Delivery MAP elicited significantly higher IgG titers against CTA1 and OVA compared to the Co-Delivery MAP, likely due to enhanced adjuvant functionality. The Dual-Delivery MAP induced immune responses comparable to IM injection, indicating that sequential delivery preserves adjuvant activity and enhances immunogenicity.
Conclusions: The Dual-Delivery MAP represents a novel, modular approach for skin-targeted vaccination. By separating antigen and adjuvant into distinct patches, it improves stability, maintains adjuvant efficacy, and enables personalized vaccine administration, offering a promising strategy for effective and safe vaccination.
期刊介绍：
Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to:
-(pre)formulation engineering and processing-
computational biopharmaceutics-
drug delivery and targeting-
molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)-
pharmacokinetics, pharmacodynamics and pharmacogenetics.
Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.
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