Table 3.
A summary on the studies in delivery systems for nutraceuticals in DR-related models.
| Compound | In Vivo or In Vitro | Dosage and Administration Way | Name of the Product | Particle Size (nm) | Cell Culture/Animal Model | Effects | Improvements | Year | Refs. |
|---|---|---|---|---|---|---|---|---|---|
| Nanoemulsions | |||||||||
| Lutein | In vivo | 600 μM of lutein (p.o.) | Lutein-NEL | 110 ± 8 | Rats | / | Improve the bioaccessibility of lutein | 2021 | [163] |
| Liposomes | |||||||||
| Baicalin | In vivo | As eye drops, instilled (100 μL) in the conjunctival sac | Baicalin vesicles | 667–1341 | Rabbits | Antioxidative | Improve stabilization, sterilization endurance, and safety with pharmacokinetic superiority | 2018 | [171] |
| Epigallocatechin-5-gallate (EGCG); liposomal EGCG | In vivo | 2.5 mg/100 g b.w./day (i.p., once a day for two consecutive days before STZ administration) | Liposomal nanoformulation of EGCG | 170 | STZ-induced DR (rats) | Antioxidative | Superior antioxidant activity of L-EGCG; enhanced availability of EGCG | 2020 | [176] |
| Ellagic acid (EA) | In vitro and in vivo | 10 µg/mL | Liposomes (EA-Hb/TAT and isoDGR-Lipo) | 170.77–212.90 | Hyperglycemia/hypoxia-induced injury in ARPE-19 cells/HUVECs | Ameliorated retinal structure, antioxidative, downregulated the expression of GFAP, HIF-1α, VEGF, and p-VEGFR2 | Better cellular uptake; potential as eye drops; co-loaded with Hb | 2023 | [180] |
| 5 mg/kg (i.v., once every 3 days for 6 weeks); as eye drops | db/db mice | ||||||||
| Lisosan G | In vivo | 1 g kg/day (p.o.) | Lisosan G in liposomes (LipoLG) | ~130 | STZ-induced DR (mice) | Restored retinal function, downregulated typical molecular hallmarks of DR (oxidative stress, inflammation, glial reaction, apoptosis, VEGF expression, and BRB breakdown) | Good entrapment efficiency of Lisosan G, good storage stability | 2023 | [178] |
| Quercetin | In vivo | 50, 200 mg/kg (p.o.) | Pegylated quercetin liposomes (Q-PEGL) | 128.8 ± 18.05 | STZ-induced diabetic nephropathy (rats) | FBG level ↓, antioxidative | Maintaining higher quercetin concentrations in plasma | 2020 | [175] |
| SNEDDS | |||||||||
| Resveratrol | In vitro | As eye drops | RSV-SNEDDS | <100 | Rabbit corneal epithelial cell line (SIRC) | / | Improved solubility, stability, and bioavailability; reduced drug loss during storage | 2024 | [182] |
| Solid lipid nanoparticles | |||||||||
| Quercetin | In vivo | 5 and 10 mg/kg (i.p. for 21 days) | Nano-formulation of quercetin (NQ) | 157.1–528.2 | STZ-induced DR (zebrafish) | Neuroprotective, ameliorated DR | Good bioavailability | 2020 | [183] |
| Polymeric nanocarriers | |||||||||
| Curcumin | In vivo | nCUR (20 mg CUR equivalent/kg/day, p.o.) with or without subcutaneous insulin (2 IU/rat/day) | PLGA-GA2-CUR nanoparticles (nCUR) | 261 | STZ-induced DR (rats) | Anti-inflammatory and anti-hyperglycemic; prevented diabetic cataracts and retinopathy | Well-tolerated, lower nanoparticle toxicity | 2023 | [188] |
| Lutein | In vitro | Micellar lutein (10 μM) or LNCs (10 μM lutein) (0, 3, 6, 12, 18, 24 h) | Double-layered chitosan–sodium alginate-based lutein nanocarrier (LNCs) | 95 ± 5 | H2O2/CoCl2-treated ARPE-19 cells | Anti-angiogenic, antioxidative | Increased cellular uptake, slowed and controlled lutein release; LNCs improved the cellular efficacy of lutein by curtailing oxidative stress. | 2023 | [186] |
| Lutein | In vitro and in vivo | 0, 1, 5, 10, 15, 15, 20, or 50 μM for 24 h | Lutein-loaded chitosan–sodium alginate-based nanocarrier systems (LNCs) | 98 ± 5 | H2O2-treated ARPE-19 cells | Antioxidative | Longer half-life of lutein, higher bioavailability | 2021 | [185] |
| 600 μM (p.o.) | STZ-induced DR (rat) | ||||||||
| Resveratrol | In vitro | Intravitreal injection | PMs-Rv-Rh6G | 3579 ± 0.19 | HRPE cells (D407) | Anti-VEGF, anti-inflammatory | High-efficiency encapsulation of resveratrol | 2019 | [187] |
| Metal-based and biopolymeric nanoparticles | |||||||||
| Resveratrol | In vitro | / | NIR light-responsive thermoplasmonic-triggered release of therapeutic resveratrol-carrying polymeric microcapsules (MC) | <100 | HRPE cells (D407) | Anti-VEGF | Light-triggered delivery and release; high stability; great biocompatibility | 2022 | [194] |
| Metal-based nanoparticles | |||||||||
| Ellagic acid (EA) | In silico docking study | / | Nano-encapsulated ellagic acid (NEA) | 161–297 | / | Inhibitory actions on aldose reductase and α-glucosidase | Improved the solubility and biological responses besides minimizing toxicity and degradation | 2020 | [190] |
| Rutin | In vivo | Rutin (10 mg/kg/day) or AuNPsR (0.6 mL/day); (p.o. for 7 days) | AuNPsR | 8–22 (mean = 15) | STZ-induced DR (rats) | Antioxidative, improved fundus appearance of retinal arterioles, decreased MDA, and increased antioxidant capacity | Improved bioavailability, green synthesis | 2023 | [193] |
| Quercetin | In vitro and in vivo | Fe-Quer NZs (25, 50, 100, or 200 µg/mL) for 48 h | Ultrasmall Fe-Quer nanozymes (NZs) | 5–10 | HG-induced injury in HUVECs and monkey choroid–retinal endothelial cells (RF) | Protected against inflammation, oxidative stress damage, microvascular leakage, and angiogenesis | Exhibiting excellent water dispersibility and efficient ROS scavenging ability | 2023 | [191] |
| 60 mg/kg (p.o.) | STZ-induced DR (rats) | ||||||||
Abbreviations: Administration routes: i.p., intraperitoneal injection; i.v., intravenous injection; p.o., per os (by mouth). Others: BRB, blood–retinal barrier; FBG, fasting blood glucose; GFAP, glial fibrillary acidic protein; Hb, hemoglobin; HIF-1α, hypoxia-inducible factor-1 alpha; p-VEGFR2, phosphorylated vascular endothelial growth factor receptor 2; STZ, streptozotocin; VEGF, vascular endothelial growth factor; ↓: down-regulated.