Innovations in Oral and Buccal Drug Delivery: Mucoadhesive Systems, Controlled Release, and Translational Applications

Due to its non-invasive nature and ease of administration, the buccal and oral mucosal delivery route has been proposed not only for localized effects but, more importantly, for achieving systemic drug delivery. This administration route has enabled the effective management of a wide range of pathologies: examples include cardiovascular emergencies treated with nitroglycerin, hypertension management with calcium channel blockers, pain therapy using potent opioids such as fentanyl, as well as hormonal therapies and allergen immunotherapy.This delivery route offers significant advantages, such as bypassing hepatic first-pass metabolism and ensuring rapid absorption; however, the path toward effective administration is not without obstacles and limitations. The oral mucosa presents significant physiological barriers, such as the stratified squamous epithelium, which restricts the passage of hydrophilic macromolecules. Furthermore, the drug's contact time with the absorption site is often compromised by salivary flow (the "wash-out" effect), involuntary swallowing, and mechanical movements associated with speech and mastication. Added to these challenges is the potential for enzymatic degradation by local esterases and peptidases, as well as variability in bioavailability due to fluctuations in oral pH. To overcome these hurdles, current research is focusing on cutting-edge technological solutions.A fundamental pillar and core focus of this Research Topic is the development of advanced mucoadhesive systems for controlled release. These systems are designed not only to prolong drug residence time on the mucosa but also to ensure precise and constant release kinetics, thereby maximizing therapeutic efficacy. Concurrently, the formulation of nanoparticles (lipid or polymeric) and the use of permeability enhancement strategies - encompassing both chemical enhancers and physical techniques- work in synergy with controlled-release systems to allow for both local and systemic effects. This paves the way for the administration of drugs previously deemed impossible to deliver via this route.The success of translational medicine in this field depends strictly on the quality of preclinical and clinical study models. Current research utilizes sophisticated in vitro cellular models and ex vivo models that accurately mimic the properties of the human epithelium.Clinical trials have demonstrated how innovation in formulation design - ranging from bioerodible films to medicated lollipops - can drastically improve patient compliance, particularly in pediatric and geriatric populations. Furthermore, the integration of advanced imaging technologies now allows for real-time monitoring of drug distribution and release at the tissue level.This collection aims to explore these recent advancements, with particular emphasis on controlled-release technologies. It also looks toward future perspectives, such as the application of Artificial Intelligence for formulation optimization and the new frontiers of transmucosal treatments. By bridging experimental, clinical, and translational research, we intend to provide a comprehensive overview of how oral and buccal administration is redefining the standards of modern pharmacological therapy through controlled release.This Research Topic welcomes basic and translational articles focused on the use of innovative therapeutic strategies for buccal and transmucosal drug delivery. Potential topics include, but are not limited to:· New insights into the physiological and molecular barriers involved in transport across the oral mucosa, with a particular focus on the overcoming of the stratified squamous epithelium by macromolecules.· Identification of new target therapies and candidate molecules for transmucosal administration, expanding the use of buccal and transmucosal routes to complex macromolecules, including peptides, hormones, and advanced treatments.· Use of traditional drugs nanotechnologically formulated into innovative systems - such as lipid and polymer nanoparticles, liposomes, and nanovesicles - capable of protecting the active ingredient from salivary degradation and effectively delivering it to the systemic target site.· New nanomaterials and mucoadhesive systems for the sublingual and buccal delivery of a wide range of synthetic and natural drugs, ensuring controlled release and enhanced adhesion to the absorption site.· Innovative treatments for oral cavity pathologies and adjunctive therapies for local conditions, utilizing specialized transmucosal formats. Topic editors: Saturnino Marco Lupi, Luis Alberto Gaitan, Mayara Rodrigues Brandão De Paiva Source: https://www.frontiersin.org/research-topics/82441/innovations-in-oral-and-buccal-drug-delivery-mucoadhesive-systems-controlled-release-and-translational-applications