Therapeutic effects of curcumin nanoemulsions on prostate cancer

Abstract

The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.

Keywords

curcumin / nanoemulsion / prostate cancer / anticancer efficacy / oral absorption

References

[1] AnandP, KunnumakkaraAB, NewmanRA, et al. . Bioavailability of curcumin: problems and promises. Mol Pharm, 2007, 4(6): 807-818 PMID: 17999464

[2] SunJ, BiC, ChanHM, et al. . Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability. Colloids Surf B Biointerfaces, 2013, 111(11): 367-375 PMID: 23856543

[3] KanaiM, OtsukaY, OtsukaK, et al. . A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients. Cancer Chemother Pharmacol, 2013, 71(6): 1521-1530 PMID: 23543271

[4] SinglaV, MouliVP, GargSK, et al. . Induction with NCB-02 (curcumin) enema for mild-to-moderate distal ulcerative colitis—A randomized, placebo-controlled, pilot study. J Crohns Colitis, 2014, 8(3): 208-214 PMID: 24011514

[5] NabaviSF, DagliaM, MoghaddamAH, et al. . Curcumin and liver disease: from chemistry to medicine. Compr Rev Food Sci F, 2014, 13(1): 62-77

[6] TeitenMH, GaaschtF, EifesS, et al. . Chemopreventive potential of curcumin in prostate cancer. Genes Nutr, 2010, 5(1): 61-74 PMID: 19806380

[7] NaksuriyaO, OkonogiS, SchiffelersRM, et al. . Curcumin nanoformulations: A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials, 2014, 35(10): 3365-3383 PMID: 24439402

[8] GuoH, XuY, FuQ. Curcumin inhibits growth of prostate carcinoma via miR-208-mediated CDKN1A activation. Tumor Biol, 2015, 36(11): 8511-8517

[9] YallapuMM, JaggiM, ChauhanSC. Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today, 2012, 17(1–2): 71-80 PMID: 21959306

[10] TeitenMH, EifesS, DicatoM, et al. . Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment. Toxins, 2010, 2(1): 128-162 PMID: 22069551 PMCID: 3206621

[11] HatcherH, PlanalpR, ChoJ, et al. . Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci, 2008, 65(11): 1631-1652 PMID: 18324353 PMCID: 4686230

[12] JiH, TangJ, LiM, et al. . Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin. Drug Deliv, 2016, 23(2): 459-470 PMID: 24892628

[13] YangC, SuX, LiuA, et al. . Advances in clinical study of curcumin. Curr Pharm Des, 2013, 19(1): 1966-1973 PMID: 23116307

[14] YangKY, LinLC, TsengTY, et al. . Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci, 2007, 853(1–2): 183-189 PMID: 17400527

[15] BishtS, FeldmannG, SoniS, et al. . Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. J Nanobiotechnol., 2007, 5(1): 3-10

[16] UcisikMH, KüpcüS, SchusterB, et al. . Characterization of CurcuEmulsomes: nanoformulation for enhanced solubility and delivery of curcumin. J Nanobiotechnol, 2013, 11(1): 11-37

[17] MondalG, BaruiS, SahaS, et al. . Tumor growth inhibition through targeting liposomally bound curcumin to tumor vasculature. J Control Release, 2013, 172(3): 832-840 PMID: 24036260

[18] LinM, ZhangZP, ZhaoLY, et al. . Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv Drug Deliv Rev, 2013, 65(6): 880-890

[19] LuJL, WangJC, ZhaoSX, et al. . Self-microemulsifying drug delivery system (SMEDDS) improves anticancer effect of oral 9-nitrocamptothecin on human cancer xenografts in nude mice. Eur J Pharm Biopharm, 2008, 69(3): 899-907 PMID: 18434109

[20] CuiJ, YuB, ZhaoY, et al. . Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. Int J Pharm, 2009, 1371(1–2): 148-155

[21] WuX, XuJ, HuangX, et al. . Self-microemulsifying drug delivery system improves curcumin dissolution and bioavailability. Drug Dev Ind Pharm, 2011, 37(1): 15-23 PMID: 20738181

[22] DhumalDM, KothariPR, KalhapureRS, et al. . Self-microemulsifying drug delivery system of curcumin with enhanced solubility and bioavailability using a new semi-synthetic bicephalous heterolipid: in vitro and in vivo evaluation. RSC Adv, 2015, 5(110): 90295-90306

[23] LiQ, ZhaiW, JiangQ, et al. . Curcumin-piperine mixtures in self-microemulsifying drug delivery system for ulcerative colitis therapy. Int J Pharm, 2015, 490(1–2): 22-31 PMID: 25957703

[24] LinCC, LinHY, ChiMH, et al. . Preparation of curcumin microemulsions with food-grade soybean oil/lecithin and their cytotoxicity on the HepG2 cell line. Food Chem, 2014, 154: 282-290 PMID: 24518344

[25] GuanYB, QiuYH, YuanX, et al. . Prepartion and evaluation of self-microemulsifying drug delivery system of curcumin. Yi Yao Dao Bao (Chinese), 2013, 32(6): 773-777

[26] SunM, ZhaiX, XueK, et al. . Intestinal absorption and intestinal lymphatic transport of sirolimus from self-microemulsifying drug delivery systems assessed using the single-pass intestinal perfusion (SPIP) technique and a chylomicron flow blocking approach: linear correlation with oral bioavailabilities in rats. Eur J Pharm Sci, 2011, 43(3): 132-140 PMID: 21530655

[27] JainAK, ThankiK, JainS. Novel self-nanoemulsifying formulation of quercetin: Implications of pro-oxidant activity on the anticancer efficacy. Nanomedicine, 2014, 10(5): 959-969 PMID: 24407148

[28] YuH, HuangQ. Investigation of the absorption mechanism of solubilized curcumin using Caco-2 cell monolayers. J Agric Food Chem, 2011, 59(17): 9120-9126 PMID: 21805974

[29] WangYJ, PanMH, ChengAL, et al. . Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal, 1997, 15(2): 1867-1876 PMID: 9278892

[30] MulikRS, MönkkönenJ, JuvonenRO, et al. . Apoptosis-induced anticancer effect of transferrin-conjugated solid lipid nanoparticles of curcumin. Cancer Nanotechnol, 2012, 3(1–6): 65-81 PMID: 26069496 PMCID: 4452039

[31] BergonziMC, HamdouchR, MazzacuvaF, et al. . Optimization, characterization and in vitro evaluation of curcumin microemulsions. LWT-Food Sci Technol, 2014, 59(1): 148-155

[32] ZhaoG, HuangJ, XueK, et al. . Enhanced intestinal absorption of etoposide by self-microemulsifying drug delivery systems: Roles of P-glycoprotein and cytochrome P450 3A inhibition. Eur J Pharm Sci, 2013, 50(3–4): 429-439 PMID: 23981337

[33] LuY, QiJ, WuW. Absorption, disposition and pharmacokinetics of nanoemlsions. Curr Drug Metab, 2012, 13(4): 396-417 PMID: 22443535