Biomimetic and Locally Active Drug Delivery Systems for the Oral Biofilm and Periodontal Pocket: Formulation Strategies, Mechanisms and Translational Perspectives

Periodontitis and dental caries remain among the most prevalent chronic diseases, and their local treatment is limited less by the choice of active agent than by the difficulty of sustaining therapeutic concentrations against salivary and crevicular clearance, the mucosal barrier and the biofilm matrix. This narrative review (PubMed/MEDLINE, Scopus, Web of Science; 2010–2026; 118 sources) maps five mechanistic classes—mucoadhesive, in situ gelling, stimuli-responsive, nano-/microparticulate and biomimetic—alongside marketed sustained-release products onto the specific barrier each addresses and onto an explicit translational gradient. The barriers are quantified rather than described: a pocket of ≈0.5 µL perfused at ≈20 µL/h turns over some 40 times hourly, giving an intra-crevicular half-life of about one minute, and the inflamed pocket is neutral-to-alkaline (pH 7.4–8.5), so acid-triggered release is a cariogenic and not a periodontal strategy, whereas alkaline-triggered release remains an open design space. A dose calculation from these figures identifies payload potency and deliverable mass, not carrier retention, as the binding constraint on phytocompound delivery. Because no single class overcomes all barriers, hybrid nano-in-macro architectures are analysed as the structural solution. Measured against a marketed benchmark of ≈0.3 mm additional probing-depth reduction, progress now depends on consolidation rather than on novelty.