Mucoadhesive zein/beta-cyclodextrin nanoparticles for the buccal delivery of curcumin

Herein, we have developed sprayable dispersions of mucoadhesive nanoparticles (NPs) made of zein, a hydrophobic plant-based protein, for the buccal delivery of curcumin (CUR), a poorly water-soluble polyphenol. NPs were prepared by the liquid-liquid dispersion method using an antisolvent water solution without or with beta-cyclodextrin (CD). NPs were spherical with a monomodal size distribution, a mean size around 140 nm and low polydispersity. Excellent colloidal stability of NPs was found at room temperature for up to 1 month. CUR entrapment was found to depend mainly on the zein/CUR ratio and related to the ability of CUR to set within hydrophobic pockets in the zein matrix. CD addition generated an increase of NP zeta potential up to +60 mV, indicating that positively charged amino acids are prompted to settle on the NP surface. Fluorescence emission spectroscopy indicated that CD interacted with lipophilic amino acids of zein altering interchain interactions and formation of glutamine bridge. Because of zein/CD interactions, mainly occurring at NP periphery, the slowing down of the CUR release rate was observed too. A combination of spectroscopic techniques unequivocally showed that zein NPs strongly interacted with mucin due to electrostatic interactions. Once sprayed on a porcine buccal mucosa, zein/CD NPs securely attached to the tissue resisting repeated washing steps but did not allow CUR transmucosal permeation. Overall, these results point at zein/CD NPs as a novel mucoadhesive platform for the buccal delivery of poorly water-soluble molecules to use as both a food supplement or a drug product to achieve local effects.