Buccal drug delivery is ideal for first-pass drugs, enabling systemic delivery through the buccal mucosa while bypassing hepatic metabolism. This review highlights amphiphilic mucoadhesive films that deliver functionalized permeation enhancers and smart polymers for controlled, sustained release in the buccal environment. Buccal tissue’s layered structure, permeation barriers, saliva washout, and rapid turnover underscore the need for dual-functional systems. These systems, with mucoadhesive properties for retention and enhancers for absorption, improve drug efficacy against mucosal barriers. Smart polymers responsive to pH, temperature, enzymes, and light adjust release profiles to the local environment, enhancing therapy and reducing dosing. Advances in nanocomposite, multilayer, in situ forming films, and 3D-printed and biosensor-integrated films further boost buccal delivery. Nanocomposite films enhance bioavailability, multilayer films ensure stability, in situ films solidify for snug fit, and 3D printing allows personalized designs. Biosensors enable real-time treatment monitoring and adjustments. This review discusses formulation innovations, showing the promise of mucoadhesive and permeation-enhancing technologies for greater therapeutic efficacy, patient compliance, and clinical potential.
D. et al. (Wed,) studied this question.
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