Contemporary Formulations for Drug Delivery of Anticancer Bioactive Compounds

Author(s): Darinka G. Ackova, Katarina Smilkov, Darko Bosnakovski*.

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 14 , Issue 1 , 2019

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Background: The immense development in the field of anticancer research has led to an increase in the research of bioactive compounds with anticancer potential. It has been known that many bioactive natural compounds have low solubility (and low bioavailability) as their main drawback when it comes to the formulation and drug delivery to specific sites.

Objective: As many attempts have been made to overcome this issue, this review gives a summary of the current accomplishments regarding the development of new Drug Delivery Systems (DDSs) represented by nanoparticles (NPs) and exosomes.

Methods: We analyzed the published data concerning selected compounds that present the most prominent plant secondary metabolites with anticancer potential, specifically flavone (quercetin), isoflavone (genistein and curcumin) and stilbene (resveratrol) groups that have been formulated as NPs and exosomes. In addition, we summarized the patent literature published from 2015-2018 that address these formulations.

Results: Although the exact mechanism of action for the selected natural compounds still remains unclear, the anticancer effect is evident and the main research efforts are directed to finding the most suitable delivery systems. Recent patents in this field serve as evidence that these newly designed natural compound delivery systems could be powerful new anticancer agents in the very near future if the noted difficulties are overcome.

Conclusion: The focus of recent research is not only to clarify the exact mechanisms of action and therapeutic effects, but also to answer the issue of suitable delivery systems that can transport sufficient doses of bioactive compounds to the desired target.

Keywords: Anticancer agents, anticancer therapy, drug delivery systems, exosomes, nanoparticles, natural bioactive compounds, recent patents.

Li Z, Jiang H, Xu CM, Gu LW. A review: Using nanoparticles to enhance absorption and bioavailability of phenolic phytochemicals. Food Hydrocoll 2015; 43: 153-64.
Heleno SA, Martins A, Queiroz MJRP, Ferreira ICFR. Bioactivity of phenolic acids: Metabolites versus parent compounds: A review. Food Chem 2015; 173: 501-13.
Kinghorn AD, Su BN, Jang DS, Chang LC, Lee D, Gu JQ, et al. Natural inhibitors of carcinogenesis. Planta Med 2004; 70: 691-705.
Mehta RG, Murillo G, Naithani R, Peng X. Cancer chemoprevention by natural products: How far have we come? Pharm Res 2010; 27: 950-61.
Lippman SM, Hawk ET. Cancer prevention: From 1727 to milestones of the past 100 years. Cancer Res 2009; 69: 5269-84.
Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K. Anticancer effects of garlic and garlic-derived compounds for breast cancer control. Anti-cancer Agent Med 2011; 11(3): 249-53.
Lu J-J, Bao J-L, Chen X-P, Huang M, Wang Y-T. Alkaloids isolated from natural herbs as the anticancer agents. ECAM 2012; pp. 7-19.
Gao C, Jiang X, Wang H, Zhao Z, Wang W. Drug metabolism and pharmacokinetics of organosulfur compounds from garlic. J Drug Metab Toxicol 2013; 4: 159-64.
Nicastro HL, Ross SA, Milner JA. Garlic and onions: Their cancer prevention properties. Cancer Prev Res (Phila) 2015; 8(3): 181-9.
Fujiki H, Sueoka E, Watanabe T, Suganuma M. Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds. J Cancer Res Clin Oncol 2015; 141(9): 1511-22.
Habli Z, Toumieh G, Fatfat M, Rahal ON, Gali-Muhtasib H. Emerging cytotoxic alkaloids in the battle against cancer: Overview of molecular mechanisms. Molecules 2017; 22: 250-7.
Amin A, Gali-Muhtasib H, Ocker M, Schneider-Stock R. Overview of major classes of plant-derived anticancer drugs. Int Journal Biomed Sci 2009; 5(1): 1-11.
Unnati S, Ripal S, Sanjeev A, Niyati A. Novel anticancer agents from plant sources. Chin J Nat Medicines 2013; 11(1): 16-23.
Greenwell M, Rahman PKSM. Medicinal plants: Their use in anticancer treatment. Int J Pharm Sci Res 2015; 6(10): 4103-12.
Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliver Rev 2004; 56: 1649-59.
Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A. Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): A novel strategy for human cancer therapy. J Nanobiotechnol 2007; 5: 3-12.
Siddiqui IA, Adhami VM, Bharali DJ, Hafeez BB, Asim M, Khwaja SI, 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: 1712-6.
Oerlemans C, Bult W, Bos M, Storm G, Nijsen JFW, Hennink WE. Polymeric micelles in anticancer therapy: Targeting, imaging and triggered release. Pharm Res 2010; 27: 2569-89.
Hu B, Ting YW, Yang XQ, Tang WP, Zeng XX, Huang QR. Nanochemoprevention byencapsulation of (-)-epigallocatechin-3-gallate with bioactive peptides/chitosan nanoparticles forenhancement of its bioavailability. Chem Commun 2012; 48: 2421-3.
Aqil F, Munagala R, Jeyabalan J, Vadhanam MV. Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Lett 2013; 334(1): 133-41.
Watkins R, Wu L, Zhang C, Davis RM. Natural product-based nanomedicine: Recent advances and issues. Int J Nanomed 2015; 10: 6055-74.
Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm 2015; 93: 52-79.
Palazzolo S, Bayda S, Hadia M, Caligiuri I, Corona G, Toffoli G, et al. The clinical translation of organic nanomaterials for cancer therapy: A focus on polymeric nanoparticles, micelles, liposomes and exosomes. Curr Med Chem 2017; 24: 1-44.
Rasouli H, Farzaei MH, Mansouri K, Mohammadzadeh S, Khodarahmi R. Plant cell cancer: May natural phenolic compounds prevent onset anddevelopment of plant cell malignancy? A literature review. Molecules 2016; 21(9): 1104-11.
Farzaei MH, Bahramsoltani R, Rahimi R. Phytochemicals as adjunctive with conventional anticancer therapies. Curr Pharm Res 2016; 22(27): 4201-18.
Davatgaran-Taghipour Y, Masoomzadeh S, Farzaei MH, Bahramsoltani R, Karimi-Soureh Z, Rahimi R, et al. Polyphenol nanoformulations for cancer therapy: Experimental evidence and clinical perspective. Int J Nanomed 2017; 12: 2689-702.
Shih H, Pickwell GV, Quattrochi LC. Differential effects of flavonoid compounds on tumorpromoter-induced activation of the human CYP1A2 enhancer. Arch Biochem 2000; 373: 287-94.
Mendoza E, Burd R. Quercetin as a systemic chemopreventative agent: Structural and functional mechanisms. Mini Rev Med Chem 2011; 11: 1216-21.
Sak K. Site-specific anticancer effects of dietary flavonoid quercetin. Nutr Cancer 2014; 66: 177-93.
Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett 2008; 269(2): 315-25.
Minaei A, Sabzichi M, Ramezani F, Hamishehkar H, Samadi N. Co-delivery with nano-quercetin enhances doxorubicin-mediated cytotoxicity against MCF-7 cells. Mol Biol Rep 2016; 43(2): 99-105.
Khan F, Niaz K, Maqbool F, Ismail Hassan F, Abdokkahi M, Naqulapalli Venkata KC, et al. Molecular targets underlying the anticancer effects of quercetin: An update. Nutrients 2016; 8: 529-35.
Li Y, Bhuiyan M, Sarkar FH. Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein. Int J Oncol 1999; 15: 525-33.
Sarkar FH, Li Y. Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev 2002; 21: 265-80.
Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett 2008; 269: 226-42.
Li Q-S, Li C-Y, Li Z-L, Zhu H-L. Genistein and its synthetic analogs as anticancer agents. Antixancer Agents Med Chem 2012; 12: 271-81.
Li HQ, Luo Y, Qiao CH. The meshanisms of anticancer agents by genistein and synthetic derivatives of isoflavone. Mini Rev Med Chem 2012; 12(4): 350-62.
Lee J-Y, Kim HS, Song Y-S. Genistein as potential anticancer agent against ovarian cancer. J Tradit Complement Med 2012; 2(2): 96-104.
Spagnuolo C, Russo GL, Orhan IE, Habtemariam S, Daglia M, Sureda A, et al. Genistein and cancer: Current status, challenges, and future directions. Adv Nutr 2015; 6: 408-19.
Maheshwari R, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: A short review. Life Sci 2006; 78: 2081-7.
Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 2008; 10: 511-45.
Bar-Sela G, Epelbaum R, Schaffer M. Curcumin as an anti-cancer agent: Review of the gap between basic and clinical applications. Curr Med Chem 2010; 17: 190-7.
Davis CD, Ross SA. Evidence for dietary regulation of microRNAexpression in cancer cells. Nutr Rev 2008; 66: 477-82.
Sun M, Estrov Z, Ji Y, Coombes KR, Harris DH, Kurzrock R. Curcumin (diferuloylmethane) alters the expression profiles of micro RNAs in human pancreatic cancer cells. Mol Cancer Ther 2008; 7: 464-73.
Zaman MS, Chauhan N, Yallapu MM, Gara RK, Maher DM, Kumari S, et al. Curcumin nanoformulation for cervical cancer treatment. Sci Rep 2016; 6: 20051-9.
Xie M, Fan D, Zhao Z, Li Z, Li G, Chen Y, et al. Nano-curcumin prepared via supercritical: Improved anti-bacterial, anti-oxidant and anti-cancer effcacy. Int J Pharm 2015; 496(2): 732-40.
Kubota T, Uemura Y, Kobayashi M, Taguchi H. Combined effects of resveratrol and paclitaxel on lung cancer cells. Anticancer Res 2003; 23: 4039-46.
Aluyen JK, Ton QN, Tran T, Yang AE, Gottlieb HB, Bellanger RA. Resveratrol: Potential as anticancer agent. J Diet Suppl 2012; 9(1): 45-6.
Britton RG, Kovoor C, Brown K. Direct molecular targets of resveratrol: Identifying key interactions to unlock complex mechanisms. Ann N Y Acad Sci 2015; 1348: 124-33.
Varoni EM, Lo Faro AF, Sharifi-Rad J, Iriti M. Anticancer mechanisms of resveratrol. Front Nutr 2016; 3: 8-16.
Diaz-Gerevini GT, Repossi G, Dain A, Tarres MC, Das UN, Eynard AR. Benefcial action of resveratrol: How and why? Nutrition 2016; 32: 174-8.
Ha D, Yang D, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: Current perspectives and future challenges. Acta Pharm Sin B 2016; 6(4): 287-96.
Lu M, Xing H, Xun Z, Yang T, Ding P, Cai C, et al. Exosome-based small RNA delivery: Progress and prospects. Asian J Pharm Sci 2018; 13(1): 1-11.
Record M, Subra C, Silvente-Poirot S, Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol 2011; 81(10): 1171-82.
Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012; 1820: 940-8.
Gjorgieva Ackova D, Smilkov K, Bosnakovski D. Cell-based anticancer drug delivery systems. In: Rahman A, Zaman K, Eds. Topics in Anti-Cancer Research. Bentham Science Publishers 2016; pp. 87-120.
Mathivanan S, Ji H, Simpson RJ. Exosomes: Extracellular organelles important in intercellular communication. J Proteomics 2010; 73(10): 1907-20.
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29(4): 341-5.
Wahlgren J, De L. Karlson T, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, et al. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 2012; 40(17): e130-8.
Maguire CA, Balaj L, Sivaraman S, Crommentuijn MH, Ericsson M, Mincheva-Nilsson L, et al. Microvesicle-associated AAV vector as a novel gene delivery system. Mol Ther 2012; 20(5): 960-71.
Robinson SM, Fan L, White SA, Charnley RM, Mann J. The role of exosomes in the pathogenesis of pancreatic ductal adenocarcin-oma. Int J Biochem Cell Biol 2016; 75: 131-9.
Zhang ZG, Chopp M. Exosomes in stroke pathogenesis and therapy. J Clin Invest 2016; 126: 1190-7.
Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, et al. A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 2010; 18(9): 1606-14.
Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 2014; 35(7): 2383-90.
Pascucci L, Cocce V, Bonomi A, Ami D, Ceccarelli P, Ciusani E, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery. J Control Release 2014; 192: 262-70.
Hosseini HM, Halabian R, Amin M, Fooladi AAI. Texosome-based drug delivery system for cancer therapy: From past to present. Cancer Biol Med 2015; 12: 150-62.
Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, et al. Development of exosome encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 2016; 12: 655-64.
Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011; 19(10): 1769-79.
Aqil F, Munagala R, Jeyabalan J, Agrawal AK, Gupta R. Exosomes for the enhanced tissue bioavailability and efficacy of curcumin. AAPS J 2017; 19(6): 1691-702.
Clinical trials website. Available at: https://clinicaltrials. gov/ct2/show/NCT01294072 (Accessed on: January 10, 2018)
Huang Q, Yu H, Ru Q. Bioavailability and delivery of nutraceuticals using nanotechnology. J Food Sci 2010; 75(1): R50-7.
Bonferoni MC, Rossi S, Sandri G, Ferrari F. Nanoparticle formulations to enhance tumor targeting of poorly soluble polyphenols with potential anticancer properties. Semin Cancer Biol 2017; 46: 205-14.
Mozafari MR, Khosravi-Darani K, Gokce Borazan G, Cui J, Pardakhty A, Yurdugul S. Encapsulation of food ingredients using nanoliposome technology. Int J Food Prop 2008; 11: 833-44.
Nam J-S, Sharma AR, Nguyen LT, Chakraborty C, Sharma G, Lee S-S. Application of bioactive quercetin in oncotherapy: From nutrition to nanomedicine. Molecules 2016; 21: 108-13.
Reis CP, Neufeld RJ, Ribeiro AJ, Veiga F, Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomed-Nanotechnol 2006; 2(1): 8-21.
Ferrari M. Cancer nanotechnology: Opportunities and challenges. Nat Rev Cancer 2005; 5(3): 161-71.
Fang Z, Bhandari B. Encapsulation of polyphenols: A review. Trends Food Sci Tech 2010; 21(10): 510-23.
Summerlin N, Qu Z, Pujara N, Sheng Y, Jambhrunkar S, McGuckin M, et al. Colloidal mesoporous silica nanoparticles enhance the biologicalactivity of resveratrol. Colloids Surf B Biointerfaces 2016; 144: 1-7.
Zhao QS, Hu LL, Wang ZD, Li ZP, Wang AW, Liu J. Resveratrol-loaded folic acid-grafted dextran stearate submicron particles exhibits enhanced antitumor efficacy in non-small cell lung cancers. Mater Sci Eng C 2017; 72: 185-91.
Bu L, Gan L-C, Guo X-Q, Chen F-Z, Song Q. Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma. Int J Pharm 2013; 452(1-2): 355-62.
Sarkar A, Ghosh S, Chowdhury S, Pandey B, Sil PC. Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells. Biochim Biophys Acta 2016; 1860(10): 2065-75.
Hu X, Ning P, Zhang R, Yang Y, Li L, Xiao X. Anticancer effect of folic acid modified tumor-targeting quercetin lipid nanoparticle. Int J Clin Exp Med 2016; 9(9): 17195-202.
Pang X, Lu Z, Du H, Yang X, Zhai G. Hyaluronic acid-quercetin conjugate micelles: Synthesis, characterization, in vitro and in vivo evaluation. Colloids Surf B Biointerfaces 2014; 123: 778-86.
Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell 1990; 61(7): 1303-13.
Cai L, Yu R, Hao X, Ding X. Folate Receptor-targeted bioflavonoid genistein-loaded chitosan nanoparticles for enhanced anticancer effect in cervical cancers. Nanoscale Res Lett 2017; 12: 509-17.
Aditya NP, Shim M, Lee I, Lee YL, Im MH, Ko S. Curcumin and genistein coloaded nanostructured lipid carriers: In vitro digestion and antiprostate cancer activity. J Agric Food Chem 2013; 61: 1878-83.
Vecchione R, Quagliariello V, Calabria D, Calcagno V, De Luca E, Iaffaioli RV, et al. Curcumin bioavailability from oil in water nano-emulsions: In vitro and in vivo study on the dimensional, compositional and interactional dependence. J Control Release 2016; 233: 88-100.
Wan K, Sun L, Hu X, Yan Z, Yonghong Z, Zhang X, et al. Novel nanoemulsion based lipid nanosystems for favorable in vitro and in vivo characteristics of curcumin. Int J Pharm 2016; 504(1-2): 80-8.
Li S, Fang C, Zhang J, Liu B, Wei Z, Fan X, et al. Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin. Nanomedicine (Lond) 2016; 12(6): 1567-79.
Sarika PR, James NR, Kumar PR, Raj DK. Galactosylated alginate-curcumin micelles for enhanced delivery of curcumin to hepatocytes. Int J Biol Macromol 2016; 86: 1-9.
Liu L, Sun L, Wu Q, Guo W, Li L, Chen Y, et al. Curcumin loaded polymeric micelles inhibit breast tumor growth and spontaneous pulmonary metastasis. Int J Pharm 2013; 443(1-2): 175-82.
Gong C, Deng S, Wu Q, Xiang M, Wei X, Li L, et al. Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. Biomaterials 2013; 34(4): 1413-32.
Gou Q, Liu L, Wang C, Wu Q, Sun L, Yang X, et al. Polymeric nanoassemblies entrapping curcumin overcome multidrug resistance in ovarian cancer. Colloids Surf B Biointerfaces 2015; 126: 26-34.
Petrov PD, Yoncheva K, Gancheva V, Konstantinov S, Trzebicka B. Multifunctional block copolymer nanocarriers for co-delivery of silver nanoparticles and curcumin: Synthesis and enhanced efficacy against tumor cells. Eur Polym J 2016; 8: 24-33.
Naksuriya O, Shi Y, van Nostrum CF, Anuchapreeda S, Hennink WE, Okonogi S. HPMA-based polymeric micelles for curcumin solubilization and inhibition of cancer cell growth. Eur J Pharm Biopharm 2015; 94: 501-12.
Liu J, Xu L, Liu C, Zhang D, Wang S, Deng Z, et al. Preparation and characterization of cationic curcumin nanoparticles for improvement of cellular uptake. Carbohydr Polym 2012; 90(1): 16-22.
Yallapu MM, Khan S, Maher DM, Ebeling MC, Sundram V, Chauhan N, et al. Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials 2014; 35(30): 8635-48.
Jung KH, Lee JH, Park JW, Quach CHT, Moon SH, Cho YS, et al. Resveratrol-loaded polymeric nanoparticles suppress glucose metabolism and tumor growth in vitro and in vivo. Int J Pharm 2015; 478(1): 251-7.
Cao Y, Gao M, Chen C, Fan A, Zhang J, Kong D, et al. Triggered-release polymeric conjugate micelles for on- demand intracellular drug delivery. Nanotechnology 2015; 26(11): 115101.
Jose S, Anju SS, Cinu TA, Aleykutty NA, Thomas S, Souto EB. In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery. Int J Pharm 2014; 474(1-2): 6-13.
Karthikeyan S, Hoti SL, Prasad NR. Resveratrol loaded gelatin nanoparticles synergistically inhibits cell cycle progression and constitutive NF-kappa B activation, and induces apoptosis in non-small cell lung cancer cells. Biomed Pharmacother 2015; 70: 274-82.
Sanna V, Siddiqui IA, Sechi M, Mukhtar H. Resveratrol-loaded nanoparticles based on poly (epsiloncaprolactone)and poly (D,L-lactic-co-glycolic acid)-Poly(ethylene glycol) blend for prostate cancer treatment. Mol Pharm 2013; 10: 3871-81.
Guo W, Li A, Jia Z, Yuan Y, Dai H, Li H. Transferrin modified PEG-PLA-resveratrol conjugates: In vitro and in vivo studies for glioma. Eur J Pharmacol 2013; 718(1-3): 41-7.
Sun M, Nie S, Pan X, Zhang R, Fan Z, Wang S. Quercetin-nanostructured lipid carriers: Characteristics and anti-breast cancer activities in vitro. Colloids Surf B Biointerfaces 2014; 113: 15-24.
Suksiriworapong J, Phoca K, Ngamsom S, Sripha K, Moongkarndi P, Junyaprasert VB. Comparison of poly(ε-caprolactone) chain lengths of poly(e-caprolactone)-co-D-α-tocopheryl-poly(ethylene glycol) 1000 succinate nanoparticles for enhancement of quercetin delivery to SKBR3 breast cancer cells. Eur J Pharm Biopharm 2016; 101: 15-24.
Tan BJ, Liu Y, Chang KL, Lim BK, Chiu GN. Perorally active nanomicellar formulation of quercetin in the treatment of lung cancer. Int J Nanomed 2012; 7: 651-61.
Zhao J, Liu J, Wei T, Ma X, Cheng Q, Huo S, et al. Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo. Nanoscale 2016; 8: 5126-38.
Pandey SK, Patel DK, Thakur R, Mishra DP, Maiti P, Haldar C. Anti-cancer evaluation of Quercetin embedded PLA nanoparticles synthesized by emulsified nanoprecipitation. Int J Biol Macromol 2015; 75: 521-9.
Rameshthangam R, Chitra JP. Synergistic anticancer effect of green synthesized nickel nanoparticles and quercetin extracted from Ocimum sanctum leaf extract. J Mater Sci Technol 2018; 34(3): 508-22.
Sharma G, Park J, Sharma AR, Jung JS, Kim H, Chakraborty C, et al. Methoxy poly(ethylene glycol)-poly(lactide) nanoparticles encapsulating quercetin act as an effective anticancer agent by inducing apoptosis in breast cancer. Pharm Res 2015; 32(2): 723-35.
Si HY, Li DP, Wang TM, Zhang HL, Ren FY, Xu ZG, et al. Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system. J Nanosci Nanotechnol 2010; 10(4): 2325-31.
Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, et al. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells. Int J Nanomedicine 2015; 10: 2461-73.
Zhang HG. Exosomal compositions and methods for the treatment of disease. WO2011097480 2011.
Gupta RC, Mungala R, Aqil F, Jeyabalan J. Milk-derived microvesicle compositions and related methods. US9943482 (2018)
Singh PK, Prabhune AA, Ogale SB. Curcumin-sophorolipid complex. US20170224636 (2017)
Cardelli J, Dragoi AM. Cancer treatment combination compositions, methods and uses. US2010258929 (2017)
Chaudhary M. Steal targeted nanoparticles (STN) for oral drug delivery. WO2016046845 (2016)
Grattoni A, Butler EB, Palapattu G. Implantable nanochannel delivery devices. WO2016187100 (2016)
Kordas G, Efthimiadou E. Multi-responsive targeting drug delivery systems for controlled-release pharmaceutical formulation. US20160263221 (2016)
Putnam D, Crawford L. Drug delivery compositions and methods targeting P-glycoprotein.US20160279263 (2016)
Ahn D-R. Drug carrier having L-DNA nanocage structure. US20160287706 (2016)
Yan X, Fan K, Liang M. Drug carrier for tumor-specific targeted drug delivery and use thereof. US20170189343 (2017)
Trujillo K. Exosomes as a therapeutic for cancer. US20160346334 (2016) and WO2015120150 (2015)
Wiklander O. Metabolic drug loading of EVs. WO2018011128 (2018)
Wiklander O. EV-mediated delivery of binding protein-small molecule conjugates. WO2018011191 (2018)
Sordillo LA, Sordillo PP, Helson L. Use of a combination of a curcuminoid and a chemotherapeutic agent for use in treatment of glioblastoma. EP31144066 (2017)
Prud’homme RK, Sinko PJ, Stone HA, et al. Lung targeting dual drug delivery system. US20170042818 (2017)
Wu D. Flavonoid compositions for the treatment of cancer. US20170087125 (2017)
Sheu MT, Ho HO, Shen SC, Ho YS, Liu JJ. Stabilized high drug load nanocarriers, methods for their preparation and use thereof. US20170035701 (2017)
Nakase I, Yoshida T, Baileykobayashi N. Method for introducing exogenous substance into cell, and material used in said method. US20170246304 (2017)
Ganta S, Coleman TP. Drug delivery nanoemulsion systems. WO2016014337 (2016)
Iyer AK. Water soluble micellar drug delivery agents. WO2016183548 (2016)
Pattayil AJ, Jayaprabha KN. Curcumin coated magnetite nanoparticles for biomedical applications. US9468691 (2016)
Cheng J, Tong R. Nanoconjugates and nanoconjugate formulations. US9295651 (2016)
Elder EJ, Sacchetti MJ, Tlachac RJ, Zenk JL. Nanoparticle isoflavone compositions and methods for making and using the same. JP2016074683 (2016)
Labhasetwar V, Saunthararajah Y, Vijayaraghavalu S. Nanogelmediated drug delivery. US20160250152 (2016)
Prud’homme RK, Sinko PJ, Stone HA, et al. Lung targeting dual drug delivery system. US9421194 (2016)
Banerjee P, Castellanos M, Debata PR, Szerszen A, Fata JE. Activity enhancing curcumin compositions and methods of use. US20160287533 (2016)
Kalluri R, Melo S. Use of exosomes for the treatment of disease. WO2016201323 (2016)
Ranjan AP, Mukerjee A, Vishwanatha JK, Helson L. Curcumin- er, a liposomal-PLGA sustained release nanocurcumin for minimizing QT prolongation for cancer therapy. US9138411 (2015)
Cheng J, Tong R. Particulate drug delivery methods. US20150314006 (2015)
Banerjee P, Castellanos M, Debata PR, Szerszen A, Fata JE. Activity enhancing curcumin compositions and methods of use. WO2015081319 (2015)
Russo M, Spagnuolo C, Tedesco I, Russo GL. Phytochemicals in cancer prevention and therapy: Truth or dare? Toxins 2010; 2: 517-51.

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Year: 2019
Page: [19 - 31]
Pages: 13
DOI: 10.2174/1574892814666190111104834

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