Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

Wang, Fengling; Chen, Jin; Dai, Wenting; He, Zhengmin; Zhai, Dandan; Chen, Weidong

doi:10.1515/acph-2017-0021

Abstract

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (C_max), mean residence time (MRT) and total plasma clearance (CL_z/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC₅₀ value of 5.66 vs. 9.81 mg L⁻¹, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.

References

1. J. Y. Park and S. H. Jang, Epidemiology of lung cancer in Korea: Recent trends, Tuberc. Respir. Dis. (Seoul).79 (2016) 58–69; DOI: 10.4046/trd.2016.79.2.58.10.4046/trd.2016.79.2.58482318527064578
Search in Google Scholar Back to article
2. S. C. Gupta, S. Patchva, W. Koh and B. B. Aggarwal, Discovery of curcumin, a component of golden spice, and its miraculous biological activities, Clin. Exp. Pharmacol. Physiol.39 (2012) 283–299; DOI: 10.1111/j.1440-1681.2011.05648.x.10.1111/j.1440-1681.2011.05648.x328865122118895
Search in Google Scholar Back to article
3. H. Mahammedi, E. Planchat, M. Pouget, X. Durando, H. Curé, L. Guy, I. Van-Praagh, L. Savareux, M. Atger, M. Bayet-Robert, E. Gadea, C. Abrial, E. Thivat, P. Chollet and J. C. Eymard, The new combination docetaxel, prednisone and curcumin in patients with castration-resistant prostate cancer: A Pilot Phase II Study, Oncology90 (2016) 69–78; DOI: 10.1159/000441148.10.1159/00044114826771576
Search in Google Scholar Back to article
4. S. C. Gupta, G. Kismali and B. B. Aggarwal, Curcumin, a component of turmeric: from farm to pharmacy, Biofactors39 (2013) 2–13; DOI: 10.1002/biof.1079.10.1002/biof.107923339055
Search in Google Scholar Back to article
5. D. Perrone, F. Ardito, G. Giannatempo, M. Dioguardi, G. Troiano, L. Lo Russo, L. A. De, L. Laino and L. Lo Muzio, Biological and therapeutic activities, and anticancer properties of curcumin, Exp. Theor. Med.10 (2015) 1615–1623.10.3892/etm.2015.2749466530126640527
Search in Google Scholar Back to article
6. M. Kanai, Y. Otsuka, K. Otsuka, M. Sato, T. Nishimura, Y. Mori, M. Kawaguchi, E. Hatano, Y. Kodama, S. Matsumoto, Y. Murakami, A. Imaizumi, T. Chiba, J. Nishihira and H. Shibata, A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients, Cancer Chemother. Pharmacol.71 (2013) 1521–1530; DOI: 10.1007/s00280-013-2151-8.10.1007/s00280-013-2151-823543271
Search in Google Scholar Back to article
7. H. A. Hazzah, R. M. Farid, M. M. Nasra, M. A. El-Massik and O. Y. Abdallah, Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization, Int. J. Pharm.492 (2015) 248–257; DOI: 10.1016/j.ijpharm.2015.06.022.10.1016/j.ijpharm.2015.06.02226189427
Search in Google Scholar Back to article
8. F. Foglietta, L. Serpe, R. Canaparo, N. Vivenza, G. Riccio, E. Imbalzano, P. Gasco and G. P. Zara, Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines, J. Pharm. Pharm. Sci.17 (2014) 231–247.
Search in Google Scholar Back to article
9. N. Naseri, H. Valizadeh and P. Zakeri-Milani, Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application, Adv. Pharm. Bull.5 (2015) 305–313; DOI: 10.15171/apb.2015.043.10.15171/apb.2015.043461689326504751
Search in Google Scholar Back to article
10. R. H. Müller, R. Shegokar and C. M. Keck, 20 years of lipid nanoparticles (SLN and NLC): Present state of development and industrial applications, Curr. Drug. Discov. Technol.8 (2011) 207–227.10.2174/15701631179679906221291409
Search in Google Scholar Back to article
11. S. Selvamuthukumar and R. Velmurugan, Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy, Lipids Health Dis.11 (2012) 159; DOI: 10.1186/1476-511X-11-159.10.1186/1476-511X-11-159356122523167765
Search in Google Scholar Back to article
12. J. Chen, W. T. Dai, Z. M. He, L. Gao, X. Huang, J. M. Gong, H.Y. Xing and W. D. Chen, Fabrication and Evaluation of Curcumin-loaded Nanoparticles Based on Solid Lipid as a New Type of Colloidal Drug Delivery System, Indian J. Pharm. Sci.75 (2013) 178–184.
Search in Google Scholar Back to article
13. W. H. Lee, C. Y. Loo, P. M. Young, D. Traini, R. S. Mason and R. Rohanizadeh, Recent advances in curcumin nanoformulation for cancer therapy, Expert Opin. Drug Deliv.11 (2014) 1183–1201; DOI: 10.1517/17425247.2014.916686.10.1517/17425247.2014.91668624857605
Search in Google Scholar Back to article
14. Q. Y. Chen, Y. Zheng, D. M. Jiao, F.Y. Chen, H. Z. Hu, Y. Q. Wu, J. Song, J. Yan, L. J. Wu and G. Y. Lv, Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent signaling pathway, J. Nutr. Biochem.25 (2014) 177–185; DOI: 10.1016/j.jnutbio.2013.10.004.10.1016/j.jnutbio.2013.10.00424445042
Search in Google Scholar Back to article
15. M. Cao, L. Ren and G. Chen, Formulation optimization and ex vivo and in vivo evaluation of celecoxib microemulsion-based gel for transdermal delivery, AAPS PharmSciTech. (2016) Dec 2. [Epub ahead of print].10.1208/s12249-016-0667-z27914040
Search in Google Scholar Back to article
16. C. Hasovits and S. Clarke, Pharmacokinetics and pharmacodynamics of intraperitoneal cancer chemotherapeutics, Clin. Pharmacokinet.51 (2012) 203–224; DOI: 10.2165/11598890-000000000-00000.10.2165/11598890-000000000-0000022420577
Search in Google Scholar Back to article
17. S. K. Williamson, G. A. Johnson, H. A. Maulhardt, K. M. Moore, D. S. McMeekin, T. K. Schulz, G. A. Reed, K. F. Roby, C. B. Mackay, H. J. Smith, S. J. Weir, J. A. Wick, M. Markman, G. S. diZerega, M. J. Baltezor, J. Espinosa and C. J. Decedue, A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax^®) in patients with peritoneal malignancies, Cancer Chemother. Pharmacol.75 (2015) 1075–1087; DOI: 10.1007/s00280-015-2737-4.10.1007/s00280-015-2737-4450613125898813
Search in Google Scholar Back to article
18. P. Maincent, P. Thouvenot, C. Amicabile, M. Hoffman, J. Kreuter, P. Couvreur and J. P. Devissaguet, Lymphatic targeting of polymeric nanoparticles after intraperitoneal administration in rats, Pharm. Res.9 (1992) 1534–1539.10.1023/A:1015895804597
Search in Google Scholar Back to article
19. S. Kommareddy, S. B. Tiwari and M. M. Amiji, Long-circulatin polymeric nanovectors for tumorselective gene delivery, Technol. Cancer Res. Treat.4 (2005) 615–625.10.1177/15330346050040060516292881
Search in Google Scholar Back to article
20. R. Tiwari and K. Pathak, Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: comparative analysis of characteristics, pharmacokinetics and tissue uptake, Int. J. Pharm.415 (2011) 232–243; DOI: 10.1016/j.ijpharm.2011.05.044.10.1016/j.ijpharm.2011.05.04421640809
Search in Google Scholar Back to article
21. M. Fang, Y. Jin, W. Bao, H. Gao, M. Xu, D. Wang, X. Wang, P. Yao and L. Liu, In vitro characterization and in vivo evaluation of nanostructured lipid curcumin carriers for intragastric administration, Int. J. Nanomedicine7 (2012) 5395–5404; DOI: 10.2147/IJN.S36257.10.2147/IJN.S36257347160423091382
Search in Google Scholar Back to article
22. D. Zheng, W. Dai, D. Zhang, C. Duan, L. Jia, Y. Liu and Q. Zhang, In vivo studies on the oridonin-loaded nanostructured lipid carriers, Drug Deliv.19 (2012) 286–291; DOI: 10.3109/10717544.2012.704096.10.3109/10717544.2012.70409622928767
Search in Google Scholar Back to article
23. C. Mohanty and S. K. Sahoo, The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation, Biomaterials31 (2012) 6597–6611. DOI: 10.1016/j.biomaterials.2010.04.062.10.1016/j.biomaterials.2010.04.06220553984
Search in Google Scholar Back to article
24. H. Rosen and T. Abribat, The rise and rise of drug delivery, Nat. Rev. Drug Discov.4 (2005) 381–385.10.1038/nrd172115864267
Search in Google Scholar Back to article
25. D. Breznan, D. D. Das, J. S. O’Brien, C. MacKinnon-Roy, S. Nimesh, N. Q. Vuong, S. Bernatchez, N. DeSilva, Hill M, P. Kumarathasan, R. Vincent, Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines, Nanotoxicology. 1 (2017) 1–45. DOI: 10.1080/17435390.2017.1287313.10.1080/17435390.2017.128731328142331
Search in Google Scholar Back to article
26. J. H. Duan, Y. D. Zhang, S. W. Han, Y. X. Chen, B. Li, M. M. Liao, W. Chen, X. M. Deng, J. F. Zhao and B. Y. Huang, Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate) nanoparticles, Int. J. Pharm.400 (2010) 211–220.10.1016/j.ijpharm.2010.08.03320813175
Search in Google Scholar Back to article
27. S. Lev-Ari, L. Strier, D. Kazanov, O. Elkayam, D. Lichtenberg, D. Caspi and N. Arber, Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells, Rheumatology (Oxford)45 (2006) 171–177.10.1093/rheumatology/kei13216249246
Search in Google Scholar Back to article
28. S. Lev-Ari, A. Vexler, A. Starr, M. Ashkenazy-Voghera, J. Greif, D. Aderka and R. Ben-Yosef, Curcumin augments gemcitabine cytotoxic effect on pancreatic adenocarcinoma cell lines, Cancer Invest.25 (2007) 411–418.10.1080/0735790070135957717882652
Search in Google Scholar Back to article

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

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