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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Curcumin and Paclitaxel Co-loaded Heparin and Poloxamer P403 Hybrid Nanocarrier for Improved Synergistic Efficacy in Breast Cancer

Author(s): Ngoc The Nguyen*, Quynh Anh Bui, Phuong Duy Huynh, Quang Huy Nguyen, Ngoc Quyen Tran, Nguyen Thanh Viet and Dinh Trung Nguyen*

Volume 19, Issue 9, 2022

Published on: 23 May, 2022

Page: [966 - 979] Pages: 14

DOI: 10.2174/1567201819666220401095923

Price: $65

Abstract

Introduction: Multi-drug nanosystem has been employed in several therapeutic models due to the synergistic effect of the drugs and/or bioactive compounds, which help in tumor targeting and limit the usual side effects of chemotherapy.

Methods: In this research, we developed the amphiphilic Heparin-poloxamer P403 (HSP) nanogel that could load curcumin (CUR) and Paclitaxel (PTX) through the hydrophobic core of Poloxamer P403. The features of HSP nanogel were assessed through Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), differential light scattering (DLS), and critical micelle concentration (CMC). Nanogel and its dual drug-loaded platform showed high stability and spherical morphology.

Results: The drug release profile indicated fast release at pH 5.5, suggesting effective drug distribution at the tumor site. In vitro research confirms lower cytotoxicity of HSP@CUR@PTX compared to free PTX and higher inhibition effect with MCF-7 than HSP@PTX. These results support the synergism between PTX and CUR.

Conclusion: HSP@CUR@PTX suggests a prominent strategy for achieving the synergistic effect of PTX and CUR to circumvent undesirable effects in breast cancer treatment.

Keywords: Poloxamer, heparin, curcumin, paclitaxel, MCF-7, nanogel.

Graphical Abstract
[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Harbeck, N.; Gnant, M. Breast cancer. Lancet, 2017, 389(10074), 1134-1150.
[http://dx.doi.org/10.1016/S0140-6736(16)31891-8] [PMID: 27865536]
[3]
Li, C.; Ge, X.; Wang, L. Construction and comparison of different nanocarriers for co-delivery of cisplatin and curcumin: A synergistic com-bination nanotherapy for cervical cancer. Biomed. Pharmacother., 2017, 86, 628-636.
[http://dx.doi.org/10.1016/j.biopha.2016.12.042] [PMID: 28027539]
[4]
Zhao, C.Y.; Cheng, R.; Yang, Z.; Tian, Z.M. Nanotechnology for cancer therapy based on chemotherapy. Molecules, 2018, 23(4), E826.
[http://dx.doi.org/10.3390/molecules23040826] [PMID: 29617302]
[5]
Luqmani, Y.A. Mechanisms of drug resistance in cancer chemotherapy. Med. Princ. Pract., 2005, 14(Suppl. 1), 35-48.
[http://dx.doi.org/10.1159/000086183] [PMID: 16103712]
[6]
Lin, J.H.; Yamazaki, M. Clinical relevance of P-glycoprotein in drug therapy. Drug Metab. Rev., 2003, 35(4), 417-454.
[http://dx.doi.org/10.1081/DMR-120026871] [PMID: 14705869]
[7]
Russo, E.; Villa, C. Poloxamer hydrogels for biomedical applications. Pharmaceutics, 2019, 11(12), E671.
[http://dx.doi.org/10.3390/pharmaceutics11120671] [PMID: 31835628]
[8]
Zarrintaj, P.; Ramsey, J.D.; Samadi, A.; Atoufi, Z.; Yazdi, M.K.; Ganjali, M.R.; Amirabad, L.M.; Zangene, E.; Farokhi, M.; Formela, K.; Saeb, M.R.; Mozafari, M.; Thomas, S. Poloxamer: A versatile tri-block copolymer for biomedical applications. Acta Biomater., 2020, 110, 37-67.
[http://dx.doi.org/10.1016/j.actbio.2020.04.028] [PMID: 32417265]
[9]
Batrakova, E.V.; Kabanov, A.V. Pluronic block copolymers: Evolution of drug delivery concept from inert nanocarriers to biological re-sponse modifiers. J. Control. Release, 2008, 130(2), 98-106.
[http://dx.doi.org/10.1016/j.jconrel.2008.04.013] [PMID: 18534704]
[10]
Choi, J.H.; Joung, Y.K.; Bae, J.W.; Choi, J.W.; Quyen, T.N.; Park, K.D. Self-assembled nanogel of pluronic-conjugated heparin as a versatile drug nanocarrier. Macromol. Res., 2011, 19(2), 180-188.
[http://dx.doi.org/10.1007/s13233-011-0214-4]
[11]
Dang, L.H.; Vu, M.T.; Chen, J.; Nguyen, C.K.; Bach, L.G.; Tran, N.Q.; Le, V.T. Effect of ultrasonication on self-assembled nanostructures formed by amphiphilic positive-charged copolymers and negative-charged drug. ACS Omega, 2019, 4(3), 4540-4552.
[http://dx.doi.org/10.1021/acsomega.8b03346]
[12]
Pham, L.; Dang, L.H.; Truong, M.D.; Nguyen, T.H.; Le, L.; Le, V.T.; Nam, N.D.; Bach, L.G.; Nguyen, V.T.; Tran, N.Q. A dual synergistic of curcumin and gelatin on thermal-responsive hydrogel based on Chitosan-P123 in wound healing application. Biomed. Pharmacother., 2019, 117, 109183.
[http://dx.doi.org/10.1016/j.biopha.2019.109183] [PMID: 31261029]
[13]
Van Thoai, D.; Nguyen, D.T.; Dang, L.H.; Nguyen, N.H.; Nguyen, V.T.; Doan, P.; Nguyen, B.T. Le Van Thu; Tung, N.N.; Quyen, T.N. Lipophilic effect of various pluronic-grafted gelatin copolymers on the quercetin delivery efficiency in these self-assembly nanogels. J. Polym. Res., 2020, 27(12), 369.
[http://dx.doi.org/10.1007/s10965-020-02216-z]
[14]
Nguyen, D.T.; Dinh, V.T.; Dang, L.H.; Nguyen, D.N.; Giang, B.L.; Nguyen, C.T.; Nguyen, T.B.T.; Thu, L.V.; Tran, N.Q. Dual interactions of amphiphilic gelatin copolymer and nanocurcumin improving the delivery efficiency of the nanogels. Polymers (Basel), 2019, 11(5), 814.
[http://dx.doi.org/10.3390/polym11050814] [PMID: 31067644]
[15]
Nguyen, N.T.; Nguyen, N.N.T.; Tran, N.T.N.; Le, P.N.; Nguyen, T.B.T.; Nguyen, N.H.; Bach, L.G.; Doan, V.N.; Tran, H.L.B.; Le, V.T.; Tran, N.Q. Synergic activity against MCF-7 breast cancer cell growth of nanocurcumin-encapsulated and cisplatin-complexed nanogels. Molecules, 2018, 23(12), E3347.
[http://dx.doi.org/10.3390/molecules23123347] [PMID: 30567316]
[16]
Dang, L.H.; Huynh, N.T.; Pham, N.O.; Nguyen, C.T.; Vu, M.T.; Dinh, V.T.; Le, V.T.; Tran, N.Q. Injectable nanocurcumin-dispersed gelatin–pluronic nanocomposite hydrogel platform for burn wound treatment. Bull. Mater. Sci., 2019, 42(2), 71.
[http://dx.doi.org/10.1007/s12034-019-1745-0]
[17]
Karageorgis, A.; Dufort, S.; Sancey, L.; Henry, M.; Hirsjärvi, S.; Passirani, C.; Benoit, J.P.; Gravier, J.; Texier, I.; Montigon, O.; Benmerad, M.; Siroux, V.; Barbier, E.L.; Coll, J.L. An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors. Sci. Rep., 2016, 6(1), 21417.
[http://dx.doi.org/10.1038/srep21417] [PMID: 26892874]
[18]
Tong, N.A.; Nguyen, T.P.; Cuu Khoa, N.; Tran, N.Q. Aquated cisplatin and heparin-pluronic nanocomplexes exhibiting sustainable release of active platinum compound and NCI-H460 lung cancer cell antiproliferation. J. Biomater. Sci. Polym. Ed., 2016, 27(8), 709-720.
[http://dx.doi.org/10.1080/09205063.2016.1154239] [PMID: 26886825]
[19]
Zhang, X.Q.; Xu, X.; Bertrand, N.; Pridgen, E.; Swami, A.; Farokhzad, O.C. Interactions of nanomaterials and biological systems: Implica-tions to personalized nanomedicine. Adv. Drug Deliv. Rev., 2012, 64(13), 1363-1384.
[http://dx.doi.org/10.1016/j.addr.2012.08.005] [PMID: 22917779]
[20]
Yang, Z.; Sun, N.; Cheng, R.; Zhao, C.; Liu, J.; Tian, Z. Hybrid nanoparticles coated with hyaluronic acid lipoid for targeted co-delivery of paclitaxel and curcumin to synergistically eliminate breast cancer stem cells. J. Mater. Chem. B Mater. Biol. Med., 2017, 5(33), 6762-6775.
[http://dx.doi.org/10.1039/C7TB01510K] [PMID: 32264326]
[21]
Zhao, M.D.; Li, J.Q.; Chen, F.Y.; Dong, W.; Wen, L.J.; Fei, W.D.; Zhang, X.; Yang, P.L.; Zhang, X.M.; Zheng, C.H. Co-delivery of curcumin and paclitaxel by “Core-Shell” targeting amphiphilic copolymer to reverse resistance in the treatment of ovarian cancer. Int. J. Nanomedicine, 2019, 14, 9453-9467.
[http://dx.doi.org/10.2147/IJN.S224579] [PMID: 31819443]
[22]
Le, P.N.; Huynh, C.K.; Tran, N.Q. Advances in thermosensitive polymer-grafted platforms for biomedical applications. Mater. Sci. Eng. C, 2018, 92, 1016-1030.
[http://dx.doi.org/10.1016/j.msec.2018.02.006] [PMID: 30184725]
[23]
Alemi, A.; Zavar Reza, J.; Haghiralsadat, F.; Zarei Jaliani, H.; Haghi Karamallah, M.; Hosseini, S.A.; Haghi Karamallah, S. Paclitaxel and cur-cumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy. J. Nanobiotechnology, 2018, 16(1), 28.
[http://dx.doi.org/10.1186/s12951-018-0351-4] [PMID: 29571289]
[24]
Liu, Z.; Liu, D.; Wang, L.; Zhang, J.; Zhang, N. Docetaxel-loaded pluronic p123 polymeric micelles: In vitro and in vivo evaluation. Int. J. Mol. Sci., 2011, 12(3), 1684-1696.
[http://dx.doi.org/10.3390/ijms12031684] [PMID: 21673916]
[25]
Wei, Z.; Hao, J.; Yuan, S.; Li, Y.; Juan, W.; Sha, X.; Fang, X. Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: Formulation, optimization and in vitro characterization. Int. J. Pharm., 2009, 376(1-2), 176-185.
[http://dx.doi.org/10.1016/j.ijpharm.2009.04.030] [PMID: 19409463]
[26]
Eslami, P.; Rossi, F.; Fedeli, S. Hybrid nanogels: Stealth and biocompatible structures for drug delivery applications. Pharmaceutics, 2019, 11(2), E71.
[http://dx.doi.org/10.3390/pharmaceutics11020071] [PMID: 30736486]
[27]
Salmaso, S.; Caliceti, P. Stealth properties to improve therapeutic efficacy of drug nanocarriers. J. Drug Deliv., 2013, 2013, 374252.
[http://dx.doi.org/10.1155/2013/374252] [PMID: 23533769]
[28]
Kesharwani, S.S.; Kaur, S.; Tummala, H.; Sangamwar, A.T. Multifunctional approaches utilizing polymeric micelles to circumvent multidrug resistant tumors. Colloids Surf. B Biointerfaces, 2019, 173, 581-590.
[http://dx.doi.org/10.1016/j.colsurfb.2018.10.022] [PMID: 30352379]
[29]
Sakiyama-Elbert, S.E. Incorporation of heparin into biomaterials. Acta Biomater., 2014, 10(4), 1581-1587.
[http://dx.doi.org/10.1016/j.actbio.2013.08.045] [PMID: 24021232]
[30]
Gao, X.; Wang, B.; Wu, Q.; Wei, X.; Zheng, F.; Men, K.; Shi, H.; Huang, N.; Wei, Y.; Gong, C. Combined delivery and anti-cancer activity of paclitaxel and curcumin using polymeric micelles. J. Biomed. Nanotechnol., 2015, 11(4), 578-589.
[http://dx.doi.org/10.1166/jbn.2015.1964] [PMID: 26310065]
[31]
Giordano, A.; Tommonaro, G. Curcumin and cancer. Nutrients, 2019, 11(10), 2376.
[http://dx.doi.org/10.3390/nu11102376]
[32]
Zhan, Y.; Chen, Y.; Liu, R.; Zhang, H.; Zhang, Y. Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling. Arch. Pharm. Res., 2014, 37(8), 1086-1095.
[http://dx.doi.org/10.1007/s12272-013-0311-3] [PMID: 24318305]
[33]
Roni, M.A.; Kibria, G. In vitro studies of controlled release alfuzosin matrix tablets prepared with ethylcellulose and hydroxypropyl methyl-cellulose. Iranian J. Pharm. Sci., 2009, 5(2), 59-68.
[34]
Han, L.M.; Guo, J.; Zhang, L.J.; Wang, Q.S.; Fang, X.L. Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluron-ic P123. Acta Pharmacol. Sin., 2006, 27(6), 747-753.
[http://dx.doi.org/10.1111/j.1745-7254.2006.00340.x] [PMID: 16723095]
[35]
Pawar, A. Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting. Artificial Cells, Nanomedicine, and Biotechnology, 2018, 46(sup1), 347-361.
[http://dx.doi.org/10.1080/21691401.2018.1423991]
[36]
Fares, A.R.; ElMeshad, A.N.; Kassem, M.A.A. Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: Formulation, optimization using central composite design and in vivo bioavailability study. Drug Deliv., 2018, 25(1), 132-142.
[http://dx.doi.org/10.1080/10717544.2017.1419512] [PMID: 29275642]
[37]
Nguyen, T.D.; Nguyen, T.N.; Nguyen, T.T.T.; Ivanov, I.A.; Nguyen, K.C.; Tran, Q.N.; Hoang, A.N.; Utkin, Y.N. Nanoencapsulation enhances anticoagulant activity of adenosine and dipeptide IleTrp. Nanomaterials (Basel), 2019, 9(9), 1191.
[http://dx.doi.org/10.3390/nano9091191] [PMID: 31443607]
[38]
Nguyen, M.N.T.; Ho-Huynh, T.D. Selective cytotoxicity of a Vietnamese traditional formula, Nam Dia long, against MCF-7 cells by synergis-tic effects. BMC Complement. Altern. Med., 2016, 16(1), 220.
[http://dx.doi.org/10.1186/s12906-016-1212-z] [PMID: 27421261]
[39]
Martins, A.F.; Pereira, A.G.B.; Fajardo, A.R.; Rubira, A.F.; Muniz, E.C. Characterization of polyelectrolytes complexes based on N, N, N-trimethyl chitosan/heparin prepared at different pH conditions. Carbohydr. Polym., 2011, 86(3), 1266-1272.
[http://dx.doi.org/10.1016/j.carbpol.2011.06.024]
[40]
Wang, X.; Gao, Y.; Wang, W.; Qin, A.; Sun, J.Z.; Tang, B.Z. Different amine-functionalized poly (diphenylsubstituted acetylenes) from the same precursor. Polym. Chem., 2016, 7(33), 5312-5321.
[http://dx.doi.org/10.1039/C6PY01175F]
[41]
Chiş V. Molecular and vibrational structure of 2, 4-dinitrophenol: FT-IR, FT-Raman and quantum chemical calculations. Chem. Phys., 2004, 300(1-3), 1-11.
[http://dx.doi.org/10.1016/j.chemphys.2004.01.003]
[42]
Yar, M.; Shahzad, S.; Shahzadi, L.; Shahzad, S.A.; Mahmood, N.; Chaudhry, A.A.; Rehman, I.U.; MacNeil, S. Heparin binding chitosan de-rivatives for production of pro-angiogenic hydrogels for promoting tissue healing. Mater. Sci. Eng. C, 2017, 74, 347-356.
[http://dx.doi.org/10.1016/j.msec.2016.12.021] [PMID: 28254303]
[43]
Debele, T.A.; Mekuria, S.L.; Lin, S.Y.; Tsai, H.C. Synthesis and characterization of bioreducible heparin-polyethyleneimine nanogels: Appli-cation as imaging-guided photosensitizer delivery vehicle in photodynamic therapy. RSC Advances, 2016, 6(18), 14692-14704.
[http://dx.doi.org/10.1039/C5RA25650J]
[44]
Reis, E.F.; Campos, F.S.; Lage, A.P.; Leite, R.C.; Heneine, L.G.; Vasconcelos, W.L.; Lobato, Z.I.P.; Mansur, H.S. Synthesis and characteriza-tion of poly (vinyl alcohol) hydrogels and hybrids for rMPB70 protein adsorption. Mater. Res., 2006, 9(2), 185-191.
[http://dx.doi.org/10.1590/S1516-14392006000200014]
[45]
Xu, T.; Chi, B.; Chu, M.; Zhang, Q.; Zhan, S.; Shi, R.; Xu, H.; Mao, C. Hemocompatible ɛ-polylysine-heparin microparticles: A platform for detecting triglycerides in whole blood. Biosens. Bioelectron., 2018, 99, 571-577.
[http://dx.doi.org/10.1016/j.bios.2017.08.030] [PMID: 28826001]
[46]
Wang, J.; Hu, W.; Liu, Q.; Zhang, S. Dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fi-broin and chitosan. Colloids Surf. B Biointerfaces, 2011, 85(2), 241-247.
[http://dx.doi.org/10.1016/j.colsurfb.2011.02.035] [PMID: 21459560]
[47]
Peng, J.; Qi, T.; Liao, J.; Chu, B.; Yang, Q.; Li, W.; Qu, Y.; Luo, F.; Qian, Z. Controlled release of cisplatin from pH-thermal dual responsive nanogels. Biomaterials, 2013, 34(34), 8726-8740.
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.092] [PMID: 23948167]
[48]
Zhuang, W.; Ma, B.; Liu, G.; Chen, X.; Wang, Y. A fully absorbable biomimetic polymeric micelle loaded with cisplatin as drug carrier for cancer therapy. Regen. Biomater., 2018, 5(1), 1-8.
[http://dx.doi.org/10.1093/rb/rbx012] [PMID: 29423262]
[49]
Ding, H.; Yong, K.T.; Law, W.C.; Roy, I.; Hu, R.; Wu, F.; Zhao, W.; Huang, K.; Erogbogbo, F.; Bergey, E.J.; Prasad, P.N. Non-invasive tumor detection in small animals using novel functional Pluronic nanomicelles conjugated with anti-mesothelin antibody. Nanoscale, 2011, 3(4), 1813-1822.
[http://dx.doi.org/10.1039/c1nr00001b] [PMID: 21365120]
[50]
Zhu, Y.; Noy, J.M.; Lowe, A.B.; Roth, P.J. The synthesis and aqueous solution properties of sulfobutylbetaine (co) polymers: Comparison of synthetic routes and tuneable upper critical solution temperatures. Polym. Chem., 2015, 6(31), 5705-5718.
[http://dx.doi.org/10.1039/C5PY00160A]
[51]
Mahou, R.; Wandrey, C. Versatile route to synthesize heterobifunctional poly (ethylene glycol) of variable functionality for subsequent pegylation. Polymers (Basel), 2012, 4(1), 561-589.
[http://dx.doi.org/10.3390/polym4010561]
[52]
Mulloy, B.; Forster, M.J.; Jones, C.; Davies, D.B. Nmr and molecular-modelling studies of the solution conformation of heparin. Biochem. J., 1993, 293(Pt 3), 849-858.
[http://dx.doi.org/10.1042/bj2930849] [PMID: 8352752]

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