Hybrid Mucointeractive Delivery Systems-Alternative Approaches to Mucosal Delivery

Mucosa can be found in the eyes, oral cavity, bladder, vagina, airways, and gastrointestinal tract. It is an attractive route of administration for systemic or topical delivery of therapeutics. However, the mucus layer acts as a protective barrier, limiting the amount of biomolecules that reach the underlying epithelium. Mucoadhesion, mucodiffusion, and mucolysis are well-established mucointeractive strategies that can improve therapeutic outcomes, but due to their individual limitations, the resulting delivery is often still unsatisfactory. In recent years, drug delivery systems have emerged that combine multiple mucointeractive strategies, which we define here as hybrid mucointeractive delivery systems. This work aims to provide a general overview of such drug delivery systems, which include particle-releasing macrostructures such as gels, foams, films, and fibers, as well as systems such as zeta potential-changing particles and self-emulsifying drug delivery systems. Their potential, possible future, and limitations are discussed as well.