The present research had been attempted to formulate and characterize tocotrienols-rich naringenin nanoemulgel for topical application in chronic wound conditions associated with diabetes. In due course, different phases of the nanoemulsion were chosen based on the solubility study, where combination of Capryol 90 and tocotrienols, Solutol HS15, and Transcutol P were selected as oil, surfactant, and cosurfactant, respectively. The nanoemulsions were formulated using the spontaneous emulsification method. Subsequently, Carbopols were incorporated to develop corresponding nanoemulgels of the optimized nanoemulsions. Thermodynamically stable optimized nanoemulgels were evaluated for their globule size, polydispersity index (PDI), surface charge, viscosity, mucoadhesive property, spreadability, in vitro release and release mechanism. Further, increasing polymer concentration in the nanoemulgels was reflected with the increased mucoadhesive property with corresponding decrease in the release rate of the drug. The optimized nanoemulgel (NG1) consisted of uniform dispersion (PDI, 0.452 ± 0.03) of the nanometric globules (145.58 ± 12.5) of the dispersed phase, and negative surface charge (-21.1 ± 3.32 mV) with viscosity 297,600 cP and good spreadability. In vitro release of naringenin in phosphate buffer saline revealed a sustained release profile up to a maximum of 74.62 ± 4.54% from the formulated nanoemulgel (NG1) within the time-frame of 24 h. Alternatively, the release from the nanoemulsion was much higher (89.17 ± 2.87%), which might be due to lack of polymer coating on the dispersed oil droplets. Moreover, the in vitro release kinetics from the nanoemulgel followed the first-order release and Higuchi model with non-Fickian diffusion. Therefore, encouraging results in this research is evident in bringing a promising future in wound management, particularly associated with diabetes complications.
Mucoadhesive drug delivery systems (MDDS) have emerged as an important strategy in modern pharmacology to enhance drug residence time, improve mucosal absorption, and optimize therapeutic performance across diverse administration routes. By enabling intimate and prolonged interactions with mucosal tissues, MDDS directly influence pharmacokinetic and pharmacodynamic outcomes while supporting patient-centric, non-invasive drug delivery. Recent advances in polymer engineering, surface functionalization, and formulation design have further expanded the capability of MDDS to overcome biological barriers and address key limitations associated with conventional dosage forms. This review provides a comprehensive and mechanistically driven analysis of MDDS, focusing on the fundamental principles of mucoadhesion and the physicochemical and biological factors governing adhesive strength, mucus penetration, and controlled drug release. A wide range of mucoadhesive delivery platforms, including films, gels, tablets, patches, hydrogels, and particulate systems, are discussed in relation to their structure-property-function relationships and pharmacological performance across oral, nasal, ocular, gastrointestinal, vaginal, rectal, and pulmonary routes. The role of natural, semi-synthetic, and synthetic polymers, together with advanced functionalization strategies such as thiolation, ligand incorporation, stimuli-responsive networks, and nanotechnology integration, is critically evaluated with respect to enhancing adhesion, permeability, and therapeutic efficacy. Beyond formulation design, the review emphasizes translational and drug discovery-relevant considerations, including Quality by Design (QbD), manufacturing scalability, regulatory and safety expectations, and clinically evaluated and Food and Drug Administration-approved mucoadhesive products. Selected clinical trials and case studies of successful and unsuccessful formulations are examined to highlight key challenges in clinical translation and to identify emerging opportunities. By bridging mechanistic understanding with applied pharmacology and translational development, this review positions MDDS as a versatile and clinically viable platform for advancing next-generation drug delivery strategies and accelerating their progression from discovery to patient care.