Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives

Abstract

The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed.

Keywords: bioactivity; bioavailability; chitosan nanoparticles; mucoadhesion; phytochemicals.

Figure 1

Chemical structures of selected phytochemicals reviewed in this manuscript for oral bioavailability and bioactivity after encapsulation in CS-NPs.

Figure 2

Chemical structure of chitin, chitosan, and protonated chitosan.

Figure 3

Chemical structures of different chitosan derivatives prepared by the functionalization of native chitosan.

Figure 4

Diagrammatic representation of different controlled release mechanisms of phytochemicals from CS-NPs. (a) The diffusion of phytochemicals from the matrix of CS-NPs. (b) The swelling mechanism of phytochemical release from CS-NPs. In this mechanism, the cross-linked chain of CS absorbs a large quantity of water from the biological system without dissolving, which leads to the widening of pores, resulting in the diffusion of the encapsulated phytochemical. (c) The erosion mechanism of phytochemical release from CS-NPs. In the erosion process, CS loses polymer mass with time in the biological fluids, which results in controlled release of the encapsulated phytochemical from the CS-NPs.

Figure 5

Schematic illustrations of (A) the structure of the intestinal epithelium, (B) different transport mechanisms of pure phytochemicals/synthetic drugs/macromolecules, and (C) different transport mechanisms of phytochemical-loaded CS-NPs.