Development of Nanoparticle-Based Mucosal Drug Delivery Systems for Controlling Pharmacokinetic Behaviors

Abstract

The mucosal layer in various mucosal tissues acts as a barrier that protects the epithelial membrane from foreign substances. However, in the process of mucosal absorption of drugs, the mucus layer, a smart biological sieve to particles and molecules, can be an obstacle to effective drug delivery. Recently, functional nanoparticles (NPs) have attracted considerable interest in the field of biopharmaceutical science owing to their delivery potential and effectiveness. Among various pharmaceutical technologies, mucopenetrating NPs (MPP) and mucoadhesive NPs (MAP) are viable dosage options for controlling pharmacokinetic behavior by modifying drug absorption from the mucosal site. MPP and MAP can rapidly deliver encapsulated drugs to the absorption site by passing through the mucus layer and/or retaining NPs near the absorption membrane, possibly resulting in better drug delivery than that of conventional approaches. Modifying the surface properties of NPs is critical for determining their potential diffusiveness within the mucus layer owing to various types of interactions between the mucosal components and the surface of NPs. Additionally, the physiological characteristics of the mucus layer (thickness, viscosity, and turnover time) differ depending on the mucosal site. Thus, a deeper understanding of the design of NPs and the functional properties of the administration site is essential for developing mucosal drug delivery systems (mDDS) to maximize the potential of target drugs. This review summarizes the basic information and functions of the mucosal layer, highlights the recent progress in designing functional NPs for mDDS, and discusses the advantages and disadvantages of mucosal administration at major mucosal sites.