Delivering flavonoids into solid tumors using nanotechnologies

Expert Opinion on Drug Delivery

Volumn 10, Issue 10, 2013, Pages 1411-1428

  Wang, Shengpeng ^a   Zhang, Jinming ^a   Chen, Meiwan ^a   Wang, Yitao ^a  

^a University of Macau   (Macao)

Author keywords

Bioavailability; Flavonoids; Nanotechnologies; Solid tumors

Indexed keywords

2 OCTYLDODECANOL; APIGENIN; BOVINE SERUM ALBUMIN; CATECHIN; CHITOSAN; CYTARABINE; DAIDZEIN; DAUNORUBICIN; DOXORUBICIN; DRUG CARRIER; EPICATECHIN; EPIGALLOCATECHIN GALLATE; FLAVONOID; FLUOROURACIL; GENISTEIN; LIPOSOME; MACROGOL; MEDIUM CHAIN TRIACYLGLYCEROL; NANOCARRIER; NANORIBBON; NICKEL NANOPARTICLE; PACLITAXEL; PHOSPHATIDYLCHOLINE; POLYGLACTIN; POLYLACTIDE; POLYSACCHARIDE; QUERCETIN; RUTOSIDE; SILIBININ; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; ARTICLE; BLADDER CANCER; BREAST CANCER; CANCER THERAPY; CLINICAL TRIAL (TOPIC); COLORECTAL CANCER; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG METABOLISM; DRUG SOLUBILITY; ENDOMETRIUM CANCER; ESOPHAGUS CANCER; FOLLICULAR LYMPHOMA; HUMAN; LIPOSOMAL DELIVERY; LIVER CELL CARCINOMA; LUNG CANCER; LUNG SMALL CELL CANCER; MULTIPLE MYELOMA; NANOEMULSION; NANOENCAPSULATION; NANOTECHNOLOGY; NONHUMAN; OVARY CARCINOMA; PLASMACYTOMA; PROSTATE CANCER; SARCOIDOSIS; SKIN CANCER; SOLID TUMOR; UTERINE CERVIX CANCER;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CATECHIN; DRUG DELIVERY SYSTEMS; FLAVONOIDS; GENISTEIN; HUMANS; NANOTECHNOLOGY; NEOPLASMS; QUERCETIN;

EID: 84884559103     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2013.807795     Document Type: Article

References (170)

1. Kidd PM. Bioavailability and activity of phytosome complexes from botanical polyphenols: The silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev 2009;14(3):226-46
2. Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: Potential use for cancer prevention. Nutr Cancer 2010;62(1):1-20
3. Botelho MA, Rao VS, Carvalho CB, et al. Lippia sidoides and Myracrodruon urundeuva gel prevents alveolar bone resorption in experimental periodontitis in rats. J Ethnopharmacol 2007;113(3):471-8
4. Botelho MA, Rao VS, Montenegro D, et al. Effects of a herbal gel containing carvacrol and chalcones on alveolar bone resorption in rats on experimental periodontitis. Phytother Res 2008;22(4):442-9
5. Pan MH, Ho CT. Chemopreventive effects of natural dietary compounds on cancer development. Chem Soc Rev 2008;37(11):2558-74
6. Bravo L. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998;56(11):317-33
7. Ververidis F, Trantas E, Douglas C, et al. Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health. Biotechnol J 2007;2(10):1214-34
8. Weng CJ, Yen GC. Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev 2012;31(1-2):323-51
9. Tan AC, Konczak I, Sze DM, Ramzan I. Molecular pathways for cancer chemoprevention by dietary phytochemicals. Nutr Cancer 2011;63(4):495-505
10. Boyle P, Levin B. International Agency for Research on Cancer: World Cancer Report 2008. France: Lyon 2008
11. Ehrlich P. The collected papers of Paul Ehrlich. London: Pergamon 1960; 3 p
12. Willett WC. Balancing life-style and genomics research for disease prevention. Science 2002;296(5568):695-8
13. Mazza GJ. Anthocyanins and heart health. Ann Ist Super Sanita 2007;43(4):369-74
14. Leonarduzzi G, Testa G, Sottero B, et al. Design and development of nanovehiclebased delivery systems for preventive or therapeutic supplementation with flavonoids. Curr Med Chem 2010;17(1):74-95
15. Wang SW, Kulkarni KH, Tang L, et al. Disposition of flavonoids via enteric recycling: UDP-glucuronosyltransferase (UGT) 1As deficiency in Gunn rats is compensated by increases in UGT2Bs activities. J Pharmacol Exp Ther 2009;329(3):1023-31
16. Clere N, Faure S, Martinez MC, Andriantsitohaina R. Anticancer properties of flavonoids: Roles in various stages of carcinogenesis. Cardiovasc Hematol Agents Med Chem 2011;9(2):62-77
17. Manach C, Williamson G, Morand C, et al. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005;81(1 Suppl):230S-42S
18. Hollman PC, van Trijp JM, Buysman MN, et al. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 1997;418(1-2):152-6
19. Setchell KD, Faughnan MS, Avades T, et al. Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women. Am J Clin Nutr 2003;77(2):411-19
20. Xu X, Wang HJ, Murphy PA, et al. Daidzein Is a More Bioavailable Soymilk Isoflavone Than Is Genistein in Adult Women. Journal of Nutrition 1994;124(6):825-32
21. Goldberg DM, Yan J, Soleas GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem 2003;36(1):79-87
22. Huang X, Wu Z, Gao W, et al. Polyamidoamine dendrimers as potential drug carriers for enhanced aqueous solubility and oral bioavailability of silybin. Drug Dev Ind Pharm 2011;37(4):419-27
23. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003;3(10):768-80
24. Neuhouser ML. Dietary flavonoids and cancer risk: Evidence from human population studies. Nutr Cancer 2004;50(1):1-7
25. Theodoratou E, Kyle J, Cetnarskyj R, et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2007;16(4):684-93
26. Chun OK, Floegel A, Chung SJ, et al. Estimation of antioxidant intakes from diet and supplements in U.S. adults. J Nutr 2010;140(2):317-24
27. Ren W, Qiao Z, Wang H, et al. Flavonoids: Promising anticancer agents. Med Res Rev 2003;23(4):519-34
28. WHO. Diet, nutrition and the prevention of chronic diseases: Report of a joint WHO/FAO expert consultation. World Health Organization, Geneva 2003. Available at: Http://whqlibdoc.who. int/trs/WHO-trs-916.pdf
29. NCI. National Cancer Institute Health Information Tip Sheet: Diet and Disease. US National Institute of Health 2009. Available at: Http://www.cancer.gov
30. Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem 2007;18(7):427-42 chemopreventive activities of representative flavonoids. 31. Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev 2011;5(9):1-12
31. Kandaswami C, Lee LT, Lee PP, et al. The antitumor activities of flavonoids. In Vivo 2005;19(5):895-909
32. Ramos S. Cancer chemoprevention and chemotherapy: Dietary polyphenols and signalling pathways. Mol Nutr Food Res 2008;52(5):507-26
33. Keller RB. Flavonoids: Biosynthesis, Biological Effects and Dietary Sources. New york: Nova Science Publishers 2009; 15 p
34. Amado NG, Fonseca BF, Cerqueira DM, et al. Flavonoids: Potential Wnt/betacatenin signaling modulators in cancer. Life Sci 2011;89(15-16):545-54
35. Yao H, Xu W, Shi X, Zhang Z. Dietary flavonoids as cancer prevention agents. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2011;29(1):1-31
36. Franzen CA, Amargo E, Todorovic V, et al. The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prev Res (Phila) 2009;2(9):830-41
37. Lee SJ, Lee KW, Hur HJ, et al. Phenolic phytochemicals derived from red pine (Pinus densiflora) inhibit the invasion and migration of SK-Hep-1 human hepatocellular carcinoma cells. Ann N Y Acad Sci 2007;1095:536-44
38. Slivova V, Zaloga G, DeMichele SJ, et al. Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells.
39. Lee WJ, Chen WK, Wang CJ, et al. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicol Appl Pharmacol 2008;226(2):178-91
40. Bigelow RL, Cardelli JA. The green tea catechins, (-)-Epigallocatechin-3- gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene 2006;25(13):1922-30
41. Alvarez AI, Real R, Perez M, et al. Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response. J Pharm Sci 2010;99(2):598-617
42. Morris ME, Zhang S. Flavonoid-drug interactions: Effects of flavonoids on ABC transporters. Life Sci 2006;78(18):2116-30
43. Molnar J, Engi H, Hohmann J, et al. Reversal of multidrug resitance by natural substances from plants. Curr Top Med Chem 2010;10(17):1757-68
44. Bansal T, Jaggi M, Khar RK, Talegaonkar S. Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy. J Pharm Pharm Sci 2009;12(1):46-78
45. Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochem Pharmacol 2011;82(12):1807-21
46. Jagtap S, Meganathan K, Wagh V, et al. Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases. Curr Med Chem 2009;16(12):1451-62
47. Shankar S, Suthakar G, Srivastava RK. Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front Biosci 2007;12:5039-51
48. Ahmad N, Gupta S, Mukhtar H. Green tea polyphenol epigallocatechin-3- gallate differentially modulates nuclear factor kappaB in cancer cells versus normal cells. Arch Biochem Biophys 2000;376(2):338-46
49. Pan MH, Chiou YS, Wang YJ, et al. Multistage carcinogenesis process as molecular targets in cancer chemoprevention by epicatechin-3-gallate. Food Funct 2011;2(2):101-10
50. Shankar S, Ganapathy S, Hingorani SR, Srivastava RK. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci 2008;13:440-52
51. Mukhtar H, Ahmad N. Tea polyphenols: Prevention of cancer and optimizing health. Am J Clin Nutr 2000;71(6 Suppl):1698S-702S; discussion 703S-4S
52. Prasain JK, Barnes S. Metabolism and bioavailability of flavonoids in chemoprevention: Current analytical strategies and future prospectus. Mol Pharm 2007;4(6):846-64
53. Gee JM, DuPont MS, Rhodes MJ, Johnson IT. Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med 1998;25(1):19-25
54. Hu M. Commentary: Bioavailability of flavonoids and polyphenols: Call to arms. Mol Pharm 2007;4(6):803-6
55. Jager AK, Saaby L, Flavonoids and the CNS. Molecules. 2011;16(2):1471-85
56. Kottra G, Daniel H. Flavonoid glycosides are not transported by the human Na+/glucose transporter when expressed in Xenopus laevis oocytes, but effectively inhibit electrogenic glucose uptake. J. Pharmacol. Exp. Therap. 2007;322:829-35
57. Crozier A, Del Rio D, Clifford MN. Bioavailability of dietary flavonoids and phenolic compounds. Mol Aspects Med 2010;31(6):446-67
58. Hollman PCH. Absorption, bioavaila bility, and metabolism of flavonoids. Arch. Physiol. Biochem. 2004;42:74-83
59. Meyer UA. Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm 1996;24(5):449-59
60. Liu Z, Hu M. Natural polyphenol disposition via coupled metabolic pathways. Expert Opin Drug Metab Toxicol 2007;3(3):389-406
61. Hu M, Li XL. Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications. New York: John Wiley & Sons 2011; 91 p
62. Joseph TB, Wang SW, Liu X, et al. Disposition of flavonoids via enteric recycling: Enzyme stability affects characterization of prunetin glucuronidation across species, organs, and UGT isoforms. Mol Pharm 2007;4(6):883-94
63. Jeong EJ, Liu X, Jia X, et al. Coupling of conjugating enzymes and efflux transporters: Impact on bioavailability and drug interactions. Curr Drug Metab 2005;6(5):455-68
64. Monagas M, Urpi-Sarda M, Sanchez-Patan F, et al. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct 2010;1(3):233-53
65. King RA, Broadbent JL, Head RJ. Absorption and excretion of the soy isoflavone genistein in rats. J Nutr 1996;126(1):176-82
66. Setchell KD, Brown NM, Desai P, et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 2001;131(4 Suppl):1362S-75S
67. Chen J, Lin H, Hu M. Metabolism of flavonoids via enteric recycling: Role of intestinal disposition. J Pharmacol Exp Ther 2003;304(3):1228-35
68. Jia X, Chen J, Lin H, Hu M. Disposition of flavonoids via enteric recycling: Enzyme-transporter coupling affects metabolism of biochanin A and formononetin and excretion of their phase II conjugates. J Pharmacol Exp Ther 2004;310(3):1103-13
69. Wang SW, Chen J, Jia X, et al. Disposition of flavonoids via enteric recycling: Structural effects and lack of correlations between in vitro and in situ metabolic properties. Drug Metab Dispos 2006;34(11):1837-48
70. Liu X, Tam VH, Hu M. Disposition of flavonoids via enteric recycling: Determination of the UDPglucuronosyltransferase isoforms responsible for the metabolism of flavonoids in intact Caco-2 TC7 cells using siRNA. Mol Pharm 2007;4(6):873-82
71. Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 2010;148(2):135-46
72. Wang S, Wu X, Tan M, et al. Fighting fire with fire: Poisonous Chinese herbal medicine for cancer therapy. J Ethnopharmacol 2012;140(1):33-45
73. Namiki Y, Fuchigami T, Tada N, et al. 75. Wang M, Thanou M. Targeting nanoparticles to cancer. Pharmacol Res 2010;62(2):90-9
74. Ferrari M. Cancer nanotechnology: Opportunities and challenges. Nat Rev Cancer 2005;5(3):161-71
75. Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2002;2(10):750-63
76. Jain RK. The next frontier of molecular medicine: Delivery of therapeutics. Nat Med 1998;4(6):655-7
77. Rahman M, Ahmad MZ, Kazmi I, et al. Advancement in multifunctional nanoparticles for the effective treatment of cancer. Expert Opin Drug Deliv 2012;9(4):367-81
78. Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles: Nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci 2009;30(11):592-9
79. Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med 2012;63:185-98
80. Zamboni WC, Torchilin V, Patri AK, et al. Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance. Clin Cancer Res 2012;18(12):3229-41
81. Bhattacharjee H, Balabathula P, Wood GC. Targeted nanoparticulate drugdelivery systems for treatment of solid tumors: A review Ther Deliv. 2010;1(5):713-34
82. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 1986;46(12 Pt 1):6387-92
83. Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 2001;74(1-3):47-61
84. Torchilin V. Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev 2011;63(3):131-5
85. Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov 2003;2(5):347-60
86. Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat Rev Drug Discov 2008;7(9):771-82
87. Torchilin VP, Trubetskoy VS. Which polymers can make nanoparticulate drug carriers long-circulating? Adv Drug Del Rev 1995;16(2-3):141-55
88. Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes: Improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci U S A 1991;88(24):11460-4
89. Blanco E, Hsiao A, Mann AP, et al. Nanomedicine in cancer therapy: Innovative trends and prospects. Cancer Sci 2011;102(7):1247-52
90. Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 1998;279(5349):377-80
91. Akers WJ, Zhang Z, Berezin M, et al. Targeting of alpha(nu)beta(3)- integrins expressed on tumor tissue and neovasculature using fluorescent small molecules and nanoparticles. Nanomedicine (Lond) 2010;5(5):715-26
92. Wang F, Zhang D, Zhang Q, et al. Synergistic effect of folate-mediated targeting and verapamil-mediated P-gp inhibition with paclitaxel -polymer micelles to overcome multi-drug resistance. Biomaterials 2012;32(35):9444-56
93. Gu F, Zhang L, Teply BA, et al. Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proc Natl Acad Sci U S A 2008;105(7):2586-91
94. Singh P, Gupta U, Asthana A, Jain NK. Folate and folate-PEG-PAMAM dendrimers: Synthesis, characterization, and targeted anticancer drug delivery potential in tumor bearing mice. Bioconjug Chem 2008;19(11):2239-52
95. Shekhar C. Lean and mean: Nanoparticlebased delivery improves performance of cancer drugs. Chem Biol 2009;16(4):349-50
96. Broxterman HJ, Gotink KJ, Verheul HM. Understanding the causes of multidrug resistance in cancer: A comparison of doxorubicin and sunitinib. Drug Resist Updat 2009;12(4-5):114-26
97. Szakacs G, Paterson JK, Ludwig JA, et al. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006;5(3):219-34
98. Hu CM, Zhang L. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol 2012;83(8):1104-11
99. Shapira A, Livney YD, Broxterman HJ, Assaraf YG. Nanomedicine for targeted cancer therapy: Towards the overcoming of drug resistance. Drug Resist Updat 2011;14(3):150-63
100. Saad M, Garbuzenko OB, Minko T. Codelivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer. Nanomedicine (Lond) 2008;3(6):761-76
101. Sadava D, Coleman A, Kane SE. Liposomal daunorubicin overcomes drug resistance in human breast, ovarian and lung carcinoma cells. J Liposome Res 2002;12(4):301-9
102. Riganti C, Voena C, Kopecka J, et al. Liposome-encapsulated doxorubicin reverses drug resistance by inhibiting Pglycoprotein in human cancer cells. Mol Pharm 2011;8(3):683-700
103. Perez-Vizcaino F, Duarte J, Santos-Buelga C. The flavonoid paradox: Conjugation and deconjugation as key steps for the biological activity of flavonoids. J Sci Food Agric 2012;92(9):1822-5
104. Russo M, Spagnuolo C, Tedesco I, et al. The flavonoid quercetin in disease prevention and therapy: Facts and fancies. Biochem Pharmacol 2012;83(1):6-15
105. Guo D, Wu C, Li J, et al. Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation. Nanoscale Res Lett 2009;4(12):1395-402
106. Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett 2008;269(2):315-25
107. Vargas AJ, Burd R. Hormesis and synergy: Pathways and mechanisms of quercetin in cancer prevention and management. Nutr Rev 2010;68(7):418-28
108. Araujo JR, Goncalves P, Martel F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr Res 2011;31(2):77-87
109. Date AA, Nagarsenker MS, Patere S, et al. Lecithin-based novel cationic nanocarriers (Leciplex) II: Improving therapeutic efficacy of quercetin on oral administration. Mol Pharm 2011;8(3):716-26
110. Khaled KA, El-Sayed YM, Al-Hadiya BM. Disposition of the flavonoid quercetin in rats after single intravenous and oral doses. Drug Dev Ind Pharm 2003;29(4):397-403
111. Gao Y, Wang Y, Ma Y, et al. Formulation optimization and in situ absorption in rat intestinal tract of quercetin-loaded microemulsion. Colloids Surf B Biointerfaces 2009;71(2):306-14
112. Fang R, Hao R, Wu X, et al. Bovine serum albumin nanoparticle promotes the stability of quercetin in simulated intestinal fluid. J Agric Food Chem 2011;59(11):6292-8
113. Dhawan S, Kapil R, Singh B. Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery. J Pharm Pharmacol 2011;63(3):342-51
114. Chen-yu G, Chun-fen Y, Qi-lu L, et al. Development of a Quercetin-loaded nanostructured lipid carrier formulation for topical delivery. Int J Pharm 2012;430(1-2):292-8
115. Kumari A, Yadav SK, Pakade YB, et al. Development of biodegradable nanoparticles for delivery of quercetin. Colloids Surf B Biointerfaces 2010;80(2):184-92
116. Gao L, Liu G, Wang X, et al. Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int J Pharm 2011;404(1-2):231-7
117. Sahoo NG, Kakran M, Shaal LA, et al. Preparation and characterization of quercetin nanocrystals. J Pharm Sci 2011;100(6):2379-90
118. Han Q, Yang R, Li J, et al. Enhancement of biological activities of nanostructured hydrophobic drug species. Nanoscale 2012;4(6):2078-82
119. Xiao J, Wu M, Kai G, et al. ZnO-ZnS QDs interfacial heterostructure for drug and food delivery application: Enhancement of the binding affinities of flavonoid aglycones to bovine serum albumin. Nanomedicine 2011;7(6):850-8
120. Podhajcer OL, Friedlander M, Graziani Y. Effect of liposome-encapsulated quercetin on DNA synthesis, lactate production, and cyclic adenosine 3':5'-monophosphate level in Ehrlich ascites tumor cells. Cancer Res 1980;40(4):1344-50
121. Yuan ZP, Chen LJ, Fan LY, et al. Liposomal quercetin efficiently suppresses growth of solid tumors in murine models. Clin Cancer Res 2006;12(10):3193-9
122. Wang G, Wang JJ, Yang GY, et al. Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death. Int J Nanomedicine 2012;7:271-80
123. Li H, Zhao X, Ma Y, et al. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Release 2009;133(3):238-44
124. Ghosh A, Ghosh D, Sarkar S, et al. Anticarcinogenic activity of nanoencapsulated quercetin in combating diethylnitrosamine-induced hepatocarcinoma in rats. Eur J Cancer Prev 2012;21(1):32-41
125. Goniotaki M, Hatziantoniou S, Dimas K, et al. Encapsulation of naturally occurring flavonoids into liposomes: Physicochemical properties and biological activity against human cancer cell lines. J Pharm Pharmacol 2004;56(10):1217-24
126. Wong MY, Chiu GN. Liposome formulation of co-encapsulated vincristine and quercetin enhanced antitumor activity in a trastuzumabinsensitive breast tumor xenograft model. Nanomedicine 2011;7(6):834-40
127. Khoee S, Rahmatolahzadeh R. Synthesis and characterization of pH-responsive and folated nanoparticles based on selfassembled brush-like PLGA/PEG/AEMA copolymer with targeted cancer therapy properties: A comprehensive kinetic study. Eur J Med Chem 2012;50:416-27
128. Chen D, Wan SB, Yang H, et al. EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment. Adv Clin Chem 2011;53:155-77
129. McLarty J, Bigelow RL, Smith M, et al. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila) 2009;2(7):673-82
130. Kim JW, Amin AR, Shin DM. Chemoprevention of head and neck cancer with green tea polyphenols. Cancer Prev Res (Phila) 2010;3(8):900-9
131. Suganuma M, Saha A, Fujiki H. New cancer treatment strategy using combination of green tea catechins and anticancer drugs. Cancer Sci 2011;102(2):317-23
132. Lambert JD, Lee MJ, Lu H, et al. Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following oral administration to mice. J Nutr 2003;133(12):4172-7
133. Chen L, Lee MJ, Li H, Yang CS. Absorption, distribution, elimination of tea polyphenols in rats. Drug Metab Dispos 1997;25(9):1045-50
134. Mazzanti G, Menniti-Ippolito F, Moro PA, et al. Hepatotoxicity from green tea: A review of the literature and two unpublished cases. Eur J Clin Pharmacol 2009;65(4):331-41
135. Hsieh DS, Wang H, Tan SW, et al. The treatment of bladder cancer in a mouse model by epigallocatechin-3-gallate-gold nanoparticles. Biomaterials 2011;32(30):7633-40
136. Fang JY, Lee WR, Shen SC, Huang YL. Effect of liposome encapsulation of tea catechins on their accumulation in basal cell carcinomas. J Dermatol Sci 2006;42(2):101-9
137. Smith A, Giunta B, Bickford PC, et al. Nanolipidic particles improve the bioavailability and alpha-secretase inducing ability of epigallocatechin-3- gallate (EGCG) for the treatment of Alzheimer's disease. Int J Pharm 2010;389(1-2):207-12
138. Barras A, Mezzetti A, Richard A, et al. Formulation and characterization of polyphenol-loaded lipid nanocapsules. Int J Pharm 2009;379(2):270-7
139. Dube A, Nicolazzo JA, Larson I. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+)-catechin and (-)-epigallocatechin gallate. Eur J Pharm Sci 2010;41(2):219-25
140. Dube A, Nicolazzo JA, Larson I. Chitosan nanoparticles enhance the plasma exposure of (-)-epigallocatechin gallate in mice through an enhancement in intestinal stability. Eur J Pharm Sci 2011;44(3):422-6
141. Singh M, Bhatnagar P, Srivastava AK, et al. Enhancement of cancer chemosensitization potential of cisplatin by tea polyphenols poly(lactide-coglycolide) nanoparticles. J Biomed Nanotechnol 2011;7(1):202
142. Siddiqui IA, Adhami VM, Bharali DJ, et al. Introducing nanochemoprevention as a novel approach for cancer control: Proof of principle with green tea polyphenol epigallocatechin-3-gallate. Cancer Res 2009;69(5):1712-16
143. Li B, Du W, Jin J, Du Q. Preservation of (-)-epigallocatechin-3-gallate antioxidant properties loaded in heat treated beta-lactoglobulin nanoparticles. J Agric Food Chem 2012;60(13):3477-84
144. Siddiqui IA, Mukhtar H. Nanochemoprevention by bioactive food components: A perspective. Pharm Res 2010;27(6):1054-60
145. Chang SS, O'Keefe DS, Bacich DJ, et al. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res 1999;5(10):2674-81
146. Sanna V, Pintus G, Roggio AM, et al. Targeted biocompatible nanoparticles for the delivery of (-)-epigallocatechin 3-gallate to prostate cancer cells. J Med Chem 2011;54(5):1321-32
147. Zu YG, Yuan S, Zhao XH, et al. Preparation, activity and targeting ability evaluation in vitro on folate mediated epigallocatechin-3-gallate albumin nanoparticles. Acta Pharmaceutica Sinica 2009;44(5):525-31
148. Shutava TG, Balkundi SS, Vangala P, et al. Layer-by-Layer-Coated Gelatin Nanoparticles as a Vehicle for Delivery of Natural Polyphenols. ACS Nano 2009;3(7):1877-85
149. Hu B, Ting Y, Yang X, et al. Nanochemoprevention by encapsulation of (-)-epigallocatechin-3-gallate with bioactive peptides/chitosan nanoparticles for enhancement of its bioavailability. Chem Commun (Camb) 2012;48(18):2421-3
150. Rocha S, Generalov R, Pereira Mdo C, et al. Epigallocatechin gallate-loaded polysaccharide nanoparticles for prostate cancer chemoprevention. Nanomedicine (Lond) 2011;6(1):79-87
151. Sarkar FH, Li Y. Soy isoflavones and cancer prevention. Cancer Invest 2003;21(5):744-57
152. Sarkar FH, Li Y, Wang Z, Padhye S. Lesson learned from nature for the development of novel anti-cancer agents: Implication of isoflavone, curcumin, and their synthetic analogs. Curr Pharm Des 2010;16(16):1801-12
153. Li QS, Li CY, Li ZL, Zhu HL. Genistein and its synthetic analogs as anticancer agents. Anticancer Agents Med Chem 2012;12(3):271-81
154. Pavese JM, Farmer RL, Bergan RC. Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metastasis Rev 2010;29(3):465-82
155. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997;17:353-81
156. Si HY, Li DP, Wang TM, et al. Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system. J Nanosci Nanotechnol 2010;10(4):2325-31
157. Tang J, Xu N, Ji H, et al. Eudragit nanoparticles containing genistein: Formulation, development, and bioavailability assessment. Int J Nanomedicine 2011;6:2429-35
158. Silva AP, Nunes BR, De Oliveira MC, et al. Development of topical nanoemulsions containing the isoflavone genistein. Pharmazie 2009;64(1):32-5
159. de Vargas BA, Bidone J, Oliveira LK, et al. Development of topical hydrogels containing genistein-loaded nanoemulsions. J Biomed Nanotechnol 2012;8(2):330-6
160. Shukla S, Gupta S. Apigenin: A promising molecule for cancer prevention. Pharm Res 2010;27(6):962-78
161. Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: Flavonoids and isoflavonoids. Pharmacol Ther 2001;90(2-3):157-77
162. Botelho MA, Martins JG, Ruela RS, et al. Nanotechnology in ligature-induced periodontitis: Protective effect of a doxycycline gel with nanoparticules. J Appl Oral Sci 2010;18(4):335-42
163. Gonzaga LW, Botelho MA, Queiroz DB, et al. Nanotechnology in hormone replacement therapy: Safe and efficacy of transdermal estriol and estradiol nanoparticles after 5 Years Follow-Up Study. Lat Am J Pharm 2012;31(3):442-50
164. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small 2008;4(1):26-49
165. Botelho MA, Martins JG, Ruela RS, et al. Protective effect of locally applied carvacrol gel on ligature-induced periodontitis in rats: A tapping mode AFM study. Phytother Res 2009;23(10):1439-48
166. He B, Jia Z, Du W, et al. The transport pathways of polymer nanoparticles in MDCK epithelial cells. Biomaterials 2013;34(17):4309-26
167. Zhao S, Dai W, He B, et al. Monitoring the transport of polymeric micelles across MDCK cell monolayer and exploring related mechanisms. J Control Release 2012;158(3):413-23
168. Madrigal-Carballo S, Rodriguez G, Sibaja M, et al. Chitosomes loaded with cranberry proanthocyanidins attenuate the bacterial lipopolysaccharide-induced expression of iNOS and COX-2 in raw 264.7 macrophages. J Liposome Res 2009;19(3):189-96
169. Bernkop-Schnurch A. Nanocarrier systems for oral drug delivery: Do we really need them? Eur J Pharm Sci 2013;49(2):272-7
170. Primard C, Rochereau N, Luciani E, et al. Traffic of poly(lactic acid) nanoparticulate vaccine vehicle from intestinal mucus to sub-epithelial immune competent cells. Biomaterials 2010;31(23):6060-8