Mucoadhesive cellulose Nanocrystal-chitosan nanocomposite for the delivery of hydrophobic compounds

Cellulose nanocrystals (CNC) have received much attention as a drug delivery vehicle, but their hydrophilic nature hinders hydrophobic drug loading. Ionotropic gelation using CNC and chitosan (CS) can enhance the loading/encapsulation capacity of hydrophobic compounds, improve colloidal stability, and strengthen mucoadhesion due to the cationic surface of CS. The colloidal behavior of CNC/CS nanocomposites loaded with emamectin benzoate (EMB) were elucidated by measuring the particle size, zeta potential, contact angle, and morphological structure using transmission electron microscopy. The mucoadhesive properties of the nanocomposites were evaluated by viscometric and titration method, followed by testing with zebrafish mucus. A facile and reproducible protocol to synthesize mucoadhesive CNC/CS nanocomposites that can encapsulate hydrophobic drugs is demonstrated. The optimal mass ratio for the synthesis was 1:10 (CS:CNC w/w), yielding the smallest average particle size (∼200 nm), highest zeta potentials (+40 mV), and highest drug encapsulation capacity (68.8 ± 8.7%). The steric stabilization effect of polyvinylpyrrolidone (PVP) and amphiphilic CNC stabilized the colloidal system. Importantly, the CS-coating technique enhanced the colloidal stability due to electrostatic intramolecular repulsion of the positive CS. CNC/CS nanocomposites exhibited enhanced mucoadhesive interaction with porcine mucin protein and live zebrafish mucus.