{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:19:42Z","timestamp":1792091982749,"version":"4.4.0"},"reference-count":183,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research and Graduate Studies at King Khalid University","award":["RGP2\/139\/1446"],"award-info":[{"award-number":["RGP2\/139\/1446"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Antimicrobial resistance represents one of the most formidable global health crises of the 21st century, driven by the diminishing efficacy of conventional antibiotics due to bacterial adaptation and biofilm formation. In response, antimicrobial nanoformulations have emerged as a transformative therapeutic paradigm, offering multifaceted and innovative mechanisms to combat resistant pathogens. This comprehensive review delineates the broad scope and distinct novelty of nano-enabled antimicrobial strategies, moving beyond the single-target limitations of traditional drugs. We systematically explore the diverse architectural classes of nanoformulations\u2014including metallic, polymeric, and self-assembling nanostructures\u2014and elucidate their unique mechanistic actions. These encompass (1) physical disruption of microbial membranes via electrostatic interactions; (2) catalytic generation of reactive oxygen and nitrogen species to induce an \u2018oxidative storm\u2019; (3) intracellular sabotage of essential metabolic pathways; (4) the \u2018Trojan horse\u2019 strategy for enhanced drug delivery and bioavailability; (5) efflux pump bypass to counteract a major resistance mechanism; (6) penetration and eradication of resilient biofilms; and (7) disarming pathogens through quorum sensing and virulence inhibition. Furthermore, this review highlights the immunomodulatory potential of nanoformulations; their activity beyond bacteria against fungi, viruses, and parasites; and the critical role of the nano-bio interface defined by surface physicochemistry. We also address the translational pathway, considering challenges in nanotoxicology, scalability, and regulatory approval, alongside the ecological impact and economic horizon of these technologies. This sector is projected to reach USD 5.4 to 8.96 billion by 2033 to 2034, with compound annual growth rates of 11 to 21% across antimicrobial nanomaterials, nanocoatings, and nanomedicine applications. By integrating insights from computational modeling and in silico design, this review underscores how nanoformulations leverage synergistic, multi-target approaches to overcome resistance, enhance therapeutic efficacy, and represent a significant leap forward in the future of infectious disease management. The novelty lies in the holistic and mechanistic synthesis of how nanotechnology is redefining antimicrobial warfare, offering a promising arsenal to avert a post-antibiotic era.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040423","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:53Z","timestamp":1774878113000},"page":"423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Multifaceted Mechanistic Actions of Antimicrobial Nanoformulations: Overcoming Resistance and Enhancing Efficacy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5612-6196","authenticated-orcid":false,"given":"Renuka","family":"Gudepu","sequence":"first","affiliation":[{"name":"Department of Microbiology, Pingle Government College for Women (A), Warangal 506370, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-0866","authenticated-orcid":false,"given":"Ramadevi","family":"Kyatham","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Anurag University, Hyderabad 500088, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmala Devi","family":"Ediga","sequence":"additional","affiliation":[{"name":"Department of Humanities and Basic Sciences (Physics), G. Pulla Reddy Engineering College (Autonomous), Kurnool 518007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3487-0846","authenticated-orcid":false,"given":"Geetha","family":"Penta","sequence":"additional","affiliation":[{"name":"Department of Physics, Sri Venkateswara College of Engineering, Tirupathi 517520, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Bathula","sequence":"additional","affiliation":[{"name":"Santoshimata College of Pharmacy, Nasik 423403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1585-3842","authenticated-orcid":false,"given":"Mohammed Mujahid","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-3007","authenticated-orcid":false,"given":"Mounika","family":"Sarvepalli","sequence":"additional","affiliation":[{"name":"School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3970-6065","authenticated-orcid":false,"given":"Jayarambabu","family":"Naradala","sequence":"additional","affiliation":[{"name":"Department of Physics, National Institute of Technology, Warangal 506004, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-8296","authenticated-orcid":false,"given":"Vikram","family":"Godishala","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Vaagdevi Degree and P.G. College, Warangal 506001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8361-3897","authenticated-orcid":false,"given":"Swati","family":"Dahariya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0969-6142","authenticated-orcid":false,"given":"Aditya","family":"Velidandi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Vaagdevi Degree and P.G. College, Warangal 506001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1186\/s12951-022-01573-9","article-title":"Nanobiotics against Antimicrobial Resistance: Harnessing the Power of Nanoscale Materials and Technologies","volume":"20","author":"Chakraborty","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Teng, C.-H., Wu, P.-C., Tang, S.-L., Chen, Y.-C., Cheng, M.-F., Huang, P.-C., Ko, W.-C., and Wang, J.-L. (2021). A Large Spatial Survey of Colistin-Resistant Gene Mcr-1-Carrying E. coli in Rivers across Taiwan. 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