{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:26:24Z","timestamp":1788827184407,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008627","name":"Global Affairs Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008627","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0427vvt16","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Global immunization programs continue to rely on needle-based injections despite persistent concerns regarding sharps disposal, accidental injuries, and the technical skill required for accurate intradermal administration. Needle-free jet injectors (NFJIs) are an alternative delivery method in which narrow, high-velocity liquid jets penetrate the skin without a needle. Contemporary designs, ranging from single-use disposable-syringe injectors to digitally controlled electromechanical devices, address historical safety issues and meet current WHO and FDA device expectations. Methods: Evidence from engineering analyses, preclinical modeling, and clinical trials was reviewed to characterize how jet velocity, nozzle structure, and formulation rheology influence skin penetration and drug dispersion. Published vaccine studies were examined for antibody responses, seroconversion, and reactogenicity compared with needle\u2013syringe injection. Field vaccination campaign data from national campaigns and operational reports were evaluated to describe implementation steps, acceptability, and implementation constraints. Results: Published studies evaluating vaccines, including inactivated influenza, hepatitis B, typhoid, rabies, and measles, report antibody titers and seroconversion rates after NFJI administration that are comparable to those achieved with conventional intramuscular or intradermal needle injection. Needle-free delivery was associated with operational advantages in several immunization programs, including reduced sharps waste and improved vaccination rate during high-volume immunization campaigns. Local and systemic reactogenicity follows expected patterns, with slightly higher injection-site responses in some NFJI studies. Imaging and mechanical data confirm that jet performance depends on nozzle geometry and controlled pressure pulses. At the same time, formulation stability remains a critical determinant of successful jet-based vaccine administration, particularly for protein antigens, adjuvanted formulations, and emerging mRNA vaccines that may experience transient shear stress during high-velocity injection. Evidence from vaccination campaigns further indicates that needle-free jet injectors reduce sharps waste, simplify vaccine handling and administration procedures, and support rapid vaccine delivery in large-scale immunization programs. Conclusions: Needle-free jet injectors are a practical alternative to traditional needle-based injections for some vaccines. Their main benefits include enabling intradermal dose-sparing strategies, reducing reliance on sharps disposal methods, and enabling the efficient vaccination of large groups without compromising immunogenicity. Future research should define the physicochemical stability limits of biologic formulations subjected to jet injection and evaluate digitally controlled injectors capable of precise pressure modulation and adjustable delivery parameters. In addition, needle-free jet injection eliminates needle penetration and sharps handling, which may reduce needle-associated anxiety and improve vaccine acceptability among individuals with needle aversion.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040417","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:03Z","timestamp":1774878063000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Advancing Needle-Free Jet Injectors for Global Vaccine Delivery"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-582X","authenticated-orcid":false,"given":"Peter","family":"Ikechukwu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria"},{"name":"Biopharmaceutics and Drug Delivery Lab, Faculty of Health, College of Pharmacy, Dalhousie University, P.O. Box 15000, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remigius","family":"Agu","sequence":"additional","affiliation":[{"name":"Biopharmaceutics and Drug Delivery Lab, Faculty of Health, College of Pharmacy, Dalhousie University, P.O. Box 15000, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/nri1728","article-title":"Immunization without needles","volume":"5","author":"Mitragotri","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.addr.2005.12.003","article-title":"Needle-free vaccine delivery","volume":"58","author":"Giudice","year":"2006","journal-title":"Adv. Drug Deliv. 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