{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:06:29Z","timestamp":1786374389320,"version":"build-2736575974"},"reference-count":150,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Periodontitis is a chronic inflammatory disease characterized by progressive destruction of periodontal supporting tissues. Although local drug delivery systems (LDDSs) enable site-specific therapy, their clinical efficacy remains limited by the dynamic and heterogeneous periodontal microenvironment. This review systematically delineates multiscale barriers to effective delivery, including biofilm resistance, gingival crevicular fluid (GCF)-mediated clearance, immune-mediated degradation, and impaired tissue regeneration. In response, LDDS design has evolved from passive carriers to multilevel synergistic systems, integrating responsiveness to multiple stimuli and programmed release that aligns with the antibacterial\u2013anti-inflammatory\u2013regenerative sequence. The emergence of theranostic platforms further enables real-time monitoring and feedback-controlled intervention. Despite these advances, a significant translational gap persists. Current models fail to recapitulate the polymicrobial and chronic nature of periodontitis, while overlooked\n                    <jats:italic>in vivo<\/jats:italic>\n                    phenomena, including protein corona formation and the reactive oxygen species (ROS) paradox, may compromise therapeutic outcomes. Future strategies should prioritize physiological relevance and precise spatiotemporal regulation to facilitate clinical translation of LDDSs.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1883391","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:58:48Z","timestamp":1786370328000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Local drug delivery systems for the periodontal microenvironment: from barrier penetration to multilevel synergy"],"prefix":"10.3389","volume":"17","author":[{"given":"Huilin","family":"An","sequence":"first","affiliation":[{"name":"Tianjin Stomatological Hospital and Department of Stomatology, School of Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction and Stomatology, Institute of Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Tianjin Stomatological Hospital and Department of Stomatology, School of Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction and Stomatology, Institute of Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Zhai","sequence":"additional","affiliation":[{"name":"Tianjin Stomatological Hospital and Department of Stomatology, School of Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction and Stomatology, Institute of Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tianjin Stomatological Hospital and Department of Stomatology, School of Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction and Stomatology, Institute of Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Stomatological Hospital and Department of Stomatology, School of Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction and Stomatology, Institute of Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2197779","DOI":"10.1080\/20002297.2023.2197779","article-title":"Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis","volume":"15","author":"Abdulkareem","year":"2023","journal-title":"J. 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