Table 5.

Examples of Micro-/Nano-Particulate Delivery System Containing Polyphenols.

Delivery System	Polyphenol	Formulation Composition	Preparation Method	Remarks	Ref.
Microspheres Microspheres are monolithic microcarriers with a diameter of 1–1000 μm	Ellagic acid	Liquid paraffin Span 80 Eudragit P-4135F	Solvent Evaporation	Ellagic acid was found to be protective against induced ulcerative colitis in rats and colon specific delivery was provided via microspheres.	[147]
	Pine Polyphenol	Chitosan	Emulsion Crosslinking	In vivo experiments on mice revealed improved protective effect against 60Co γ-radiation induced damages compared to free polyphenols due to improved stability and bioavailability via microspheres.	[148]
Coated Microparticles Microparticles coated with various materials (such as biodegradable, biocompatible polymers) to provide additional functionality	Resveratrol	Stearic acid Phosphatidylcholine Chitosan	Melt Emulsification	Directly nose to brain delivery of resveratrol was provided via chitosan coated lipid microparticles as demonstrated by increased drug concentration in cerebrospinal fluid in in vivo experiments.	[149]
	Curcumin	Zein Gantrez® AN119 (PVMMA, Barcelona, Spain) Eudragit® FS30D (Essen, Germany)	Spray Drying	Intestinal curcumin release and improved anti-inflammatory activity was shown by the inhibition of pro-inflammatory cytokines in macrophages. The microspheres were suggested for the treatment of inflammatory bowel diseases.	[150]
Microcapsules Microcapsules are delivery systems in which the reservoir is surrounded by a membrane shell that controls the release rate of the encapsulated cargo	Polyherbal Formulation (PHF) Extract	Gum arabic Gelatin Maltodextrin	Freeze Drying	Upon encapsulation antioxidant activity was successfully preserved. The microcapsules were found to have antidiabetic potential as α-amylase and α-glucosidase activities were inhibited, besides the in vivo studies on mice revealed improved bioavailability.	[151]
	Quercetin	Pectin Casein	Complex Coacervation-Spray Drying	Topical quercetin loaded microcapsules effectively blocked UVB induced alterations on mice. The anti-inflammatory effect of the prepared formulation was superior to free quercetin.	[152]
Polymeric nanoparticles Nanoparticles are solid colloidal systems, usually prepared from biodegradable polymers, with diameters ranging from 10 to 1000 nm. They can be prepared in the form of nanocapsules or nanospheres	Silibinin	Palmitoyl chitosan Tripolyphosphate	Ionic Gelation Method	Enhanced cytotoxicity and controlled drug release was obtain via hydrophobic chitosan based silibinin nanoparticles	[153]
	Juglans regia L. polyphenols	Polysaccharides from Hohenbuehelia serotina	Solvent evaporation	Sustained polyphenol release and improved stability against gastrointestinal conditions was achieved by encapsulation of Juglans regia L. polyphenols in polysaccharide based nanoparticles	[154]
Solid lipid nanoparticles Nanocarriers that are composed of solid lipids at body temperature and stabilized by surfactants, have a size between 50–1000 nm and can be produced on a large scale	Pomegranate Extract	Stearic acid Lecithin Tween 80	Hot Homogenization and Ultra-Sonication	Cytotoxicity studies on MCF-7 cells showed that a 47-fold reduction in IC50 levels of pure pomegranate extract was achieved with solid lipid nanoparticles	[155]
	Diosmin	Compritol ATO 888 Soy lecithin Tween 80	Hot Homogenization and Freeze Drying	Diosmin loaded solid lipid nanoparticles were superior to free diosmin in terms of antioxidant activity. The in vivo hepatic tumor incidence was also lower.	[156]
Liposomes Phospholipid based vesicular structures which can carry hydrophilic, amphiphilic, or lipophilic compounds	Resveratrol	EggPC DSPE-PEG2000, DOPE CHEMS Tf-PEG3400-PE	Thin Film Hydration Method	Transferin targeted liposomes significantly improved the tumor growth inhibition potential of resveratrol and survival in glioblastoma-bearing mice.	[157]
	Quercetin	Phosphatidylcholine Stearylamine Eudragit	Sonication	Eudragit coated liposomes improved the physical stability of quercetin in gastrointestinal conditions and showed prolonged antioxidant effect on intestinal HT-29 cells	[158]
Polymeric micelles Polymeric micelles are spherical core-corona aggregates of amphiphilic copolymers and their size is in the range of 10–100 nm	Resveratrol and Quercetin	Pluronic F127	Thin Film Hydration Method	Resveratrol and quercetin loaded polymeric micelles were effective on reducing doxorubicin hydrochloride induced cardiotoxicity in mice.	[159]
	Syringic acid	TPGS Pluronic F127 Pluronic F68	Thin Film Hydration Method	In vivo pharmacokinetic tests on rats revealed improved oral bioavailability of syringic acid after liposomal encapsulation. Enhanced cellular internalization was shown on HepG2 cells and liver targeting properties of mixed micelles was shown. Overall formulation was found to be promising for the utilization of syringic acid in functional foods.	[160]