Preparation Of Tea Polyphenol-gelatin-dextran Complex Coacervation Core Micelles With Core-shell Structure Via A Self-assembly Process

Tea polyphenol (TPP) process excellent bioactivity, such as antitumor, antioxidant, antiradiation and eliminating free radical, and it plays important roles in the prevention and treatment of several diseases such as cancer and atherosclerosis. Howerver, TPP is unstable while treated with strong acid, strong base or high temperature, and its bioavailability is low in vitro. Nanoencapsulation is a promising method to improve the bioavailability of tea polyphenol. In this work, a green and safe process was adopt to create a new kind of complex coacervation core micelles (C3Ms) based on biopolymers for tea polyphenol delivery. Firstly, gelatin-dextran conjugate is synthesized using Maillard reaction. Then the C3Ms are produced by mixing gelatin-dextran conjugate with TPP. The gelatin-dextran conjugate is charactered by SDS-PAGE and OPA assay.Viariable factors such as Maillard reaction, pH value and TPP concentration on the self-assembly of the C3Ms were investigated. The C3Ms are of nano-size (average86nm in diameter) with narrow distribution (PDI0.07). Hydrophobic interaction and hydrogen bonding instead of electrostatic interaction are attributed to the formation of the C3Ms, proved by the DLS results of C3Ms treated with destabilizing agents NaCl, SDS and urea. Transmission electron microscope (TEM) and scanning electron microscope (SEM) showed that C3Ms have a spherical shape with core-shell structure. ζ-Potential measurement suggested that the the core is composed of gelatin with TPP, while the shell is composed of dextran segments. The encapsulation efficiency of the C3Ms is pH-independent but the loading capacity is controllable and as high as360wt%(weight/weight of protein). In addition, the C3Ms show sustained release of TPP at pH5.0and pH7.4in vitro, and C3Ms can effectively prevent TPP from oxidation. Cytotoxicity experiments against MCF-7cells revealed that the C3Ms have comparable or even stronger cytotoxicity than free TPP. As dextran process abundant hydroxy group, directional drug delivery can achieve by conjugating specifically targeted groups, which will greatly contribute to the internal disease treatment.