Core–Shell\nBiopolymer Nanoparticles for Co-Delivery\nof Curcumin and Piperine: Sequential Electrostatic Deposition of Hyaluronic\nAcid and Chitosan Shells on the Zein Core

Abstract

Curcumin\nand piperine are natural nutraceuticals that exhibit synergistic\nbiological activities, but have different polarities, which can make\ntheir encapsulation within a single delivery system challenging. In\nthis study, the two bioactive components were encapsulated within\ncore–shell nanoparticles formed by a combination of antisolvent\nprecipitation and layer-by-layer deposition. Initially, strongly hydrophobic\ncurcumin (log <i>P</i> = 4.12) was embedded in the hydrophobic\ncore of zein-hyaluronic acid nanoparticles using the antisolvent precipitation\nmethod. Then, the weakly hydrophobic piperine (log <i>P</i> = 2.78) was adsorbed to the outer biopolymer shell of these nanoparticles.\nFinally, the nutraceutical-loaded particles were coated with a layer\nof chitosan by the electrostatic deposition method. The surface charge\nand coating thickness depended on the number of adsorbed layers and\nthe nature of the outer layer, being negative for hyaluronic acid\nand positive for chitosan. Low-, medium-, and high-molecular weight\nchitosan were utilized to modify the surface properties. Chitosan\nwith a low-molecular weight was selected to fabricate the core–shell\nnanoparticles because it produced small highly charged cationic particles\n(<i>d</i> = 599 nm; ζ = +38.1 mV). The encapsulation\nefficiency and loading capacities were 90.4 and 5.7% for curcumin,\nand 86.4 and 5.4% for piperine, respectively. The core–shell\nnanoparticles protected the nutraceuticals from chemical degradation\nduring light exposure, thermal processing, and storage for 2 months.\nMoreover, the nanoparticles were able to control the release of the\nbioactive components in simulated gastrointestinal conditions. Our\nresults should facilitate the development of more effective nanodelivery\nsystems for nutraceuticals that exhibit synergistic activities, but\nhave different molecular characteristics.