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Molecules 2020, 25, 4613 11 of 36 the bacterial envelope, thus facilitating the entry of antibacterial components in propolis into cells [178]. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. Alemi et al. found that the combination therapy of paclitaxel with curcumin using PEGylated noisome delivery enhanced cytotoxicity against MCF-7 cells [179]. 3.4. Protein-Based Nanoformulations Protein-based drug delivery system has high nutritional value and good functional characteristics, making it continue to develop in the food industry. 3.4.1. Casein-Based Nanoparticles Casein is the predominant protein in milk (approximately 80%), composed of αs1-, αs2-, β-, and κ-caseins, with unique hydrophilic and hydrophobic domains. These proteins self-assemble in the presence of calcium phosphate to form a spherical colloid with a diameter of 50–500 nm (average diameter 150 nm). Because the casein structure is rich in proline and can adapt to changes in its environment, it is defined as a rheological protein [180,181]. Casein has many properties that favor its use in drug delivery systems, including exceptional surface activity, excellent emulsification and self-assembly properties, and excellent water binding ability [182]. In addition, casein can interact with many molecules to form stable complexes and conjugates. These unique properties make it an excellent choice for drug delivery systems. Studies have shown that β-casein encapsulation increases the solubility of curcumin by at least 2500-fold, and the presence of this casein micellar protein enhances the cytotoxicity of the drug to human leukemia cells K-562. Furthermore, curcumin–casein showed significantly higher antioxidant activity than free curcumin [183]. Luo et al. [184] prepared rutin-sodium caseinate/pectin complex nanoparticles by acidification and heat treatment. It was found that heating not only improved the rate of nanoparticles formation, but also significantly improved the rate of rutin encapsulation. The presence of pectin delayed the hydrolysis of sodium caseinate by pepsin and allowed the controlled release of rutin in the gastrointestinal tract. In another study, rutin was coated with sodium caseinate and trehalose complex, and an analysis revealed that rutin was amorphous after addition of trehalose and pH adjustment. The powder produced by co-precipitation with sodium caseinate contained large amounts of rutin [185]. Ghayour et al. [186] encapsulated curcumin and quercetin using the coating method. The encapsulation efficiency of both compounds was greater than 90%, and their solubilities in nanoparticles were higher than those of the free polyphenol molecules. In addition, polyphenol-casein nanoparticles were more cytotoxic towards MCF-7 human breast cancer cells than unloaded molecules. 3.4.2. Gelatin Nanoparticles Gelatin is a water-soluble protein, that is prepared from collagen by acid or alkali hydrolysis (Figure 5) [187]. The US Food and Drug Administration generally believes that it is safe for use in medicine, cosmetics and food [188]. If sulfuric acid or hydrochloric acid is used to hydrolyze egg collagen, the gelatin obtained is of type A, with an isoelectric point of about 9. Correspondingly, if an alkaline solution is used to hydrolyze collagen, the gelatin produced is of type B with an isoelectric point of about 5 [189]. Gelatin is a polyamphoteric electrolyte with hydrophobic groups. Apart from being cheap and easily obtained, gelatins have good biocompatibility and biodegradability. First, because it is a deformable protein, the antigenicity of gelatin is relatively low compared with that of collagen. Second, gelatin produces no harmful by-products after enzymatic hydrolysis. In addition, the intrinsic protein structure of gelatin and the presence of many functional groups enable it to be coupled with many crosslinking agents and ligands. This has far-reaching significance for the development of targeting vectors [190,191]. Methods of preparing gelatin nanoparticles include desolvation, coacervation-phase separation, emulsification-solvent evaporation and nanoprecipitation [192–194].PDF Image | Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols
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