Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy
Abstract
:1. Introduction
2. Enhancement of Polyphenol Anticancer Effects Using DDSs
2.1. Lipid-Based System
2.1.1. Liposomes and Phytosomes
2.1.2. Nanostructured Lipid Carrier
2.2. Polymer-Based System
2.3. Protein Formulation
2.4. Other Materials
3. Consideration for Polyphenol Delivery System
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Materials | Polyphenols | Methods and Functionalization | EE * and LC ** | Particle Size | Ref. |
---|---|---|---|---|---|
Liposome | Resveratrol | PEGylation TF moiety | EE ~75% | 211.2 nm | [55] |
Peptide liposome | EE > 90% | 140 nm | [56] | ||
Curcumin | Co delivery with gefitinib PEGylation | EE > 80% | 110–130 nm | [57] | |
Phytosome | Genistein | With MCT or LCT Solvent evaporation method | EE > 95% | 150–300 nm | [61] |
Thymoquinone | Soy-phospholipid | No data | 45.6 nm | [62] | |
Curcumin | PEGylation Folate modification | LC 24.3% | 185.3 nm | [63] | |
Moringa oleifera leaf polyphenols | Soy-phosphatidylcholine Thin-layer hydration method | EE 90.23% | 296 nm | [64] | |
Nanostructured lipid particle | Curcumin | Cinnamon oil, Tween 80 PEG 200, Absorption enhancer | No data | 106 nm | [66] |
Cornus mas extract (CME) | Cubosome Glyceryl monooleate Poloxamer® 407 Eudragit® S100 | EE 95.14% LC 9.51% | 22.7 nm | [67] | |
EGCG | Arginyl-glycyl-aspartic acid (RGD) modification | EE 80% LC 75% | 85 nm | [68] | |
Apigenin | Hyaluronic acid modification Co-treatment with docetaxel | EE 70% LC 3.5% | 88 nm | [69] |
Materials | Polyphenols | Drug Release | Target | Improvement | Ref. |
---|---|---|---|---|---|
Liposome | Resveratrol | Slow release (No data) | U-87 MG human glioblastoma cells | Apoptosis 2.5-fold ↑ In vivo tumor volume 2-fold ↓ | [55] |
98% at pH 5.5 30% at pH 6.8 (~48 h) | MCF-7 breast cancer cell | Cytotoxicity 26% ↑ Apoptosis induced p53, Bax, Bcl-2, and caspase | [56] | ||
Curcumin | At pH 7.4 (~48 h) >90% (alone) >70% (with gefitinib) | PC-9 Gefitinib-resistant H1975 | Cytotoxicity 10–15% ↑ In vivo tumor growth inhibition 45% ↑ | [57] | |
Phytosome | Genistein | Unstable in pH 4.5 | Hepatocellular carcinoma | Liver toxicity reduction (AST 30%, ALT 10%) Caspase 8 ↑ Angiogenesis and invasion↓ | [61] |
Thymoquinone | >95% (45%↑) (~12 h) | A549 Human lung cancer | IC50 < 5 μM (4-fold ↓) Caspase 3 expression ↑ | [62] | |
Curcumin | 50% at pH 5.5 20% at pH 7.4 (~48 h) | HeLa cell | IC50 11.9 μg/mL (3-fold ↓) Selective accumulation in cancer 40% ↑ | [63] | |
Moringa oleifera leaf polyphenols | At pH 7.4 43% (~8 h) 53% (~72 h) | 4T1 cancer cell | Stability in gastric condition 2-fold ↑ Cytotoxicity 4-fold ↑ Proliferation inhibition (more than DOX at 100 μg/mL) | [64] | |
Nanostructured lipid particle | Curcumin | 80% at pH 1.2 >95% at pH 4.6 (~24 h) | Caco-2 Human colon cancer | Cytotoxicity 57% ↑ Cmax 5-fold ↑ AUC 4.5-fold ↑ | [66] |
Cornus mas extract (CME) | Sustained (~80 h) >90% intestinal >70% gastric | Caco-2 Human colon cancer | DPPH scavenging 27%↑ Cytotoxicity DNA fragmentation↑ Cell cycle arrest (G0-G1 phase) ↑ | [67] | |
EGCG | No data | MDA-MB-231 human breast cancer | IC50 38.8 μM (22.5% ↓) Cell cycle arrest Apoptosis ↑ | [68] | |
Apigenin | Sustained (~80 h) 90% at pH 5.5 85% at pH 7.4 | A549 Human lung cancer | IC50 23.51μM (3-fold ↓) Apoptosis 15% ↑ | [69] |
Materials | Polyphenols | Methods and Functionalization | EE * and LC ** | Particle Size | Ref. |
---|---|---|---|---|---|
Polymer | Hesperestin | Chitosan-folate conjugate Sodium tripolyphosphate (cross-linking) | EE 98% | 457 nm | [72] |
Quercetin | Eudragit S100 | EE 41.8% LC 2.2% | 66.8 nm | [73] | |
Curcumin | Spray drying HPMC15LV or PVP-K30 Lactose monohydrate | EE 13~78% | 4.8–8.3 nm | [74] | |
Phenol–yne click reaction mPEG-b-PHEMA-5HA | EE 43.4% LC 17.8% | 104 nm | [75] | ||
Quercetin | Luteinizing-hormone-releasing hormone (LHRH) ligand PLGA, PEG Co-delivery with docetaxel | EE 75.8% | 120–140 nm | [76] | |
Curcumin | Co-delivery with doxorubicin Polymeric micelle Hyaluronic acid–vitamin E succinate | EE 72% LC 8.3% | 223 nm | [77] | |
Resveratrol and curcumin | Bolton W3000 dendritic polymer solvent displacement method | No data | 130 nm | [78] | |
Protein | Resveratrol | Sericin silk protein | EE 71–75% | 200–350 nm | [81] |
Curcumin | Zein protein Dodecamer peptide (G23) Polydopamine | EE 81.7% LC 8.11% | 106.3 nm | [82] | |
Hydrophobin (HGFI) GE11 peptide | EE 88% LC 47% | 80 nm | [83] | ||
Zein protein Silk protein Co-formulation with Paclitaxel | EE 93% LC 12% | 265 nm | [84] | ||
Caseinate–chitosan Genipin cross-linking | EE 88.6% LC 4.2% | 272 nm | [85] | ||
Iron ion | Curcumin | Metal–phenolic network between EGCG and iron, coating | EE 90% LC 40% | 184.8 nm | [90] |
Nucleic acid | Tannic acid | Branched DNA, Aptamer antisense of C-raf mRNA | EE 85% | 150 nm | [93] |
Branched DNA, siPLK1 RNA A549 membrane | No data | 164.2 nm | [94] |
Materials | Polyphenols | Drug Release | Target | Improvement | Ref. |
---|---|---|---|---|---|
Polymer | Hesperestin | ~45% at pH 7.4 <20% at pH 3 (~72 h) | HCT15 Human colon cancer cell | IC50 28 μM (6.7-fold↓) Apoptosis 2.4-fold↑ Bax and Bad mRNA 35%↑ | [72] |
Quercetin | No release at < pH 4.5 (~2 h) 90% at pH 7.4 (~20 h) | CT26 colon cancer cell | IC50 0.8 μM (81-fold↓) Cell viability 40%↓ | [73] | |
Curcumin | ~28% at pH 7.4 (~90 min) | A549 Human lung cancer | Solubility 14-fold↑ IC50 44 µM (3-fold↓) | [74] | |
~25% at pH 5 ~72% at pH 7.4 (~30 h) | 4T1 cancer cell HeLa cell | IC50 4–9 µg/mL Half-life 6.16 h (14-fold↑) Tumor growth 27%↓ | [75] | ||
Quercetin | 95% at pH 7.4 (with serum, ~48 h) | PCa cell lines (PC-3 and LNCaP) | IC50 36–82%↓ Caspase 3 activation↑ in vivo tumor growth 40%↓ | [76] | |
Curcumin | ~69% at pH 4.5 ~37% at pH 7.4 (~24 h) | MCF-7 cell MCF-7/Adr cell | Reduction of drug efflux IC50 14.8-fold↓ Apoptosis 4.6-fold↑ Tumor inhibition 55.2% (2-fold↑) | [77] | |
Resveratrol and curcumin | Earlier in pH 5.4 than pH 7 | SH-SY5Y cancer cell | Cytotoxicity 37%↑ Intracellular calcium release 20%↑ Cytochrome C oxidase activation↓ Mitochondrial depolarization | [78] |
Materials | Polyphenols | Drug Release | Target | Improvement | Ref. |
---|---|---|---|---|---|
Protein | Resveratrol | 65% at pH 7.4 (~72 h, high concentration) | Caco-2 cancer cell | 97% cellular uptake after 24 h IC50 < 6% wt No toxicity to normal cell (100% wt) | [81] |
Curcumin | 80% at pH 5 45% at pH 7.4 (~48 h) | C6 glioma cell | Blood brain barrier penetration↑ (2-fold↑) Cancer proliferation and migration > 50%↓ | [82] | |
At pH 7.4 ~53% (~8 h) ~94% (~72 h) | HCT 116 cancer cell | Cellular uptake 2-fold↑ IC50 3.7 µg/mL (free curcumin is not toxic to 20 µg/mL) | [83] | ||
Sustained~180 h ~66% at pH 5 ~49% at pH 7.4 | MCF-7 breast cancer cell | IC50 0.72 µg/mL (6-fold↓) Synergistic effect (CI > 1) | [84] | ||
77% at pH 5.5 60% at pH 7.4 (~6 h) | HeLa cell A549 cell | IC50 6.5 µg/mL (35%↓) Cell surface attachment and localization | [85] | ||
Iron ion | Curcumin | 91% at pH 5 34% at pH 7.4 (~24 h) | MCF-7 human breast cancer cell | Uptake efficiency 93% after 3 h Bcl-2 down-regulation (2.6-fold↓) Bax and caspase 3 up-regulation (40%↑) | [90] |
Nucleic acid | Tannic acid | Disassembly in pH 5.5 | A549 human lung cancer cell | Cellular uptake 7-fold↑ Apoptosis 40%↑ by tannic acid and 20%↑ by therapeutic genes | [93] |
In acidic pH (when fused with endosomal/lysosomal vesicle) | A549 human lung cancer cell | Homotypic targeting (3-fold↑) Macrophage uptake 30%↓ Half-life 2.13 h (26-fold↑) Tumor growth 5-fold↓ | [94] |
Combination | DDS Method | Target/Treated Conc. | Results | Ref. |
---|---|---|---|---|
Erlotinib and resveratrol | Nanostructured lipid particle Hot homogenization method Miglyol and Precirol Poloxamer 470 Drug ratio 1:8 | A549 human lung cancer cell /E 5 µg/mL and R 40 µg/mL | Cell viability 12.6% (75%↓) Apoptosis 85.5% (20–30%↑) (Bax and p53 expression↑, Caspase 3, 8, and 9 activation↑) Cell cycle arrest 40% in G2/M phase | [110] |
Docetaxel and resveratrol | PEGylated nano-liposomes Thin-film hydration method Soy lecithin, Cholesterol, and DSPE-MPEG2000 Drug ratio 1:2 | PC3 and DU145 Human prostate cancer cell lines/D 32.3 µg/mL and R 18.3 µg/mL PC3-bearing mice/ D 10 mg/kg and R 5.65 µg/mL | IC50 (docetaxel) 1.49 µg/mL (10-fold↓) Apoptosis induction 69% (2-fold↑) Cellular uptake 3.5–5.5-fold↑ In vivo tumor growth inhibition (Volume 3-fold↓) Survival day ~42 day, (5-fold↑ than free drugs) In vivo toxicity reduction | [111] |
Cisplatin and curcumin | mPEG urethane gemini surfactant nanoparticle | MDA-MB-231 breast cancer cells/ Ci 13 µM and Cu 20 µM | Sub G1 cell ratio 20% (2–4-fold↑) Late apoptosis 59% (39–290%↑) Bax/Bcl-2 ratio 50–200%↑ | [112] |
Doxorubicin and quercetin | Polymeric nanoparticle Biotin-PEG2k-PCL5k | MCF-7 and MCF-7/ADR breast cancer cells /D 5 μg/mL and Q 11.75 μg/mL MCF-7/ADR-bearing nude mice/D 5 mg/kg and Q 11.75 mg/kg | Drug resistance↓(136-fold↓) Drug efflux 15–48%↓ P-glycoprotein activity 1.8–2.5-fold↓ In vivo tumor volume 3-fold↓ | [113] |
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Kim, K.H.; Ki, M.-R.; Min, K.H.; Pack, S.P. Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy. Antioxidants 2023, 12, 1048. https://doi.org/10.3390/antiox12051048
Kim KH, Ki M-R, Min KH, Pack SP. Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy. Antioxidants. 2023; 12(5):1048. https://doi.org/10.3390/antiox12051048
Chicago/Turabian StyleKim, Koung Hee, Mi-Ran Ki, Ki Ha Min, and Seung Pil Pack. 2023. "Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy" Antioxidants 12, no. 5: 1048. https://doi.org/10.3390/antiox12051048
APA StyleKim, K. H., Ki, M.-R., Min, K. H., & Pack, S. P. (2023). Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy. Antioxidants, 12(5), 1048. https://doi.org/10.3390/antiox12051048