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Paclitaxel loaded EDC-crosslinked fibroin nanoparticles: a potential approach for colon cancer treatment

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Abstract

Colon cancer is one of the most life-threatening cancers with high incidence and mortality rates. Current first-line treatments are ineffective and possess many unwanted effects. The off-label use of paclitaxel encapsulated in nanoparticles proves an innovative approach. In this study, we reported novel paclitaxel loaded EDC-crosslinked fibroin nanoparticles (PTX-FNPs) for anticancer purpose. The particles were formulated using desolvation method and the physicochemical properties were controlled favorably, including the particle size (300–500 nm), zeta potential (− 15 to + 30 mV), drug entrapment efficiency (75–100%), crystallinity, drug solubility (1- to 10-fold increase), dissolution profiles, stability (> 24 h in intravenous diluent and > 6 months storage at 4 °C). In in vitro study, all formulations showed no toxicity on the red blood cells, whereas retained the paclitaxel cytotoxicity on MCF-7 breast cancer and Caco-2 colon cancer cells. Interestingly, PTX-FNPs can be uptaken rapidly by the Caco-2 cells, consequently increased paclitaxel potency up to 10-fold compared to the free drug.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422. https://doi.org/10.1093/annonc/mdw235.

    Article  PubMed  Google Scholar 

  3. Temraz S, Mukherji D, Alameddine R, Shamseddine A. Methods of overcoming treatment resistance in colorectal cancer. Crit Rev Oncol Hematol. 2014;89(2):217–30. https://doi.org/10.1016/j.critrevonc.2013.08.015.

    Article  PubMed  Google Scholar 

  4. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4(4):253–65. https://doi.org/10.1038/nrc1317.

    Article  CAS  PubMed  Google Scholar 

  5. McGrogan BT, Gilmartin B, Carney DN, McCann A. Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008;1785(2):96–132. https://doi.org/10.1016/j.bbcan.2007.10.004.

    Article  CAS  PubMed  Google Scholar 

  6. Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001;37(13):1590–8. https://doi.org/10.1016/S0959-8049(01)00171-X.

    Article  CAS  PubMed  Google Scholar 

  7. Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JH. Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Res. 1996;56(9):2112–5.

    CAS  PubMed  Google Scholar 

  8. Kundranda MN, Niu J. Albumin-bound paclitaxel in solid tumors: clinical development and future directions. Drug Des Devel Ther. 2015;9:3767–77. https://doi.org/10.2147/DDDT.S88023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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.

    CAS  PubMed  Google Scholar 

  10. Ducreux M, Bennouna J, Adenis A, Conroy T, Lièvre A, Portales F, et al. Efficacy and safety of nab-paclitaxel in patients with previously treated metastatic colorectal cancer: a phase II COLO-001 trial. Cancer Chemother Pharmacol. 2017;79(1):9–16. https://doi.org/10.1007/s00280-016-3193-5.

    Article  CAS  PubMed  Google Scholar 

  11. Yusuf RZ, Duan Z, Lamendola DE, Penson RT, Seiden MV. Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets. 2003;3(1):1–19. https://doi.org/10.2174/1568009033333754.

    Article  CAS  PubMed  Google Scholar 

  12. Sheppard BC, Rutten MJ, Meichsner CL, Bacon KD, Leonetti PO, Land J, et al. Effects of paclitaxel on the growth of normal, polyposis, and cancerous human colonic epithelial cells. Cancer. 1999;85(7):1454–64. https://doi.org/10.1002/(SICI)1097-0142(19990401)85:7<1454::AID-CNCR5>3.0.CO;2-%23.

    Article  CAS  PubMed  Google Scholar 

  13. Ma P, Mumper RJ. Paclitaxel nano-delivery systems: a comprehensive review. J Nanomed Nanotechnol. 2013;4(2):1000164. https://doi.org/10.4172/2157-7439.1000164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Danhier F, Lecouturier N, Vroman B, Jérôme C, Marchand-Brynaert J, Feron O, et al. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J Control Release. 2009;133(1):11–7. https://doi.org/10.1016/j.jconrel.2008.09.086.

    Article  CAS  PubMed  Google Scholar 

  15. Forrest ML, Yáñez JA, Remsberg CM, Ohgami Y, Kwon GS, Davies NM. Paclitaxel prodrugs with sustained release and high solubility in poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelle nanocarriers: pharmacokinetic disposition, tolerability, and cytotoxicity. Pharm Res. 2008;25(1):194–206. https://doi.org/10.1007/s11095-007-9451-9.

    Article  CAS  PubMed  Google Scholar 

  16. Kim K, Kim JH, Park H, Kim YS, Park K, Nam H, et al. Tumor-homing multifunctional nanoparticles for cancer theragnosis: simultaneous diagnosis, drug delivery, and therapeutic monitoring. J Control Release. 2010;146(2):219–27. https://doi.org/10.1016/j.jconrel.2010.04.004.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang JA, Anyarambhatla G, Ma L, Ugwu S, Xuan T, Sardone T, et al. Development and characterization of a novel Cremophor EL free liposome-based paclitaxel (LEP-ETU) formulation. Eur J Pharm Biopharm. 2005;59(1):177–87. https://doi.org/10.1016/j.ejpb.2004.06.009.

    Article  CAS  PubMed  Google Scholar 

  18. Lee MK, Lim SJ, Kim CK. Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles. Biomaterials. 2007;28(12):2137–46. https://doi.org/10.1016/j.biomaterials.2007.01.014.

    Article  CAS  PubMed  Google Scholar 

  19. Constantinides PP, Lambert KJ, Tustian AK, Schneider B, Lalji S, Ma W, et al. Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel. Pharm Res. 2000;17(2):175–82. https://doi.org/10.1023/A:1007565230130.

    Article  CAS  PubMed  Google Scholar 

  20. Gibson JD, Khanal BP, Zubarev ER. Paclitaxel-functionalized gold nanoparticles. J Am Chem Soc. 2007;129(37):11653–61. https://doi.org/10.1021/ja075181k.

    Article  CAS  PubMed  Google Scholar 

  21. Hua MY, Yang HW, Chuang CK, Tsai RY, Chen WJ, Chuang KL, et al. Magnetic-nanoparticle-modified paclitaxel for targeted therapy for prostate cancer. Biomaterials. 2010;31(28):7355–63. https://doi.org/10.1016/j.biomaterials.2010.05.061.

    Article  CAS  PubMed  Google Scholar 

  22. Mottaghitalab F, Farokhi M, Shokrgozar MA, Atyabi F, Hosseinkhani H. Silk fibroin nanoparticle as a novel drug delivery system. J Control Release. 2015;206:161–76. https://doi.org/10.1016/j.jconrel.2015.03.020.

    Article  CAS  PubMed  Google Scholar 

  23. Zhao Z, Li Y, Xie MB. Silk fibroin-based nanoparticles for drug delivery. Int J Mol Sci. 2015;16(3):4880–903. https://doi.org/10.3390/ijms16034880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen M, Shao Z, Chen X. Paclitaxel-loaded silk fibroin nanospheres. J Biomed Mater Res A. 2012;100(1):203–10. https://doi.org/10.1002/jbm.a.33265.

    Article  CAS  PubMed  Google Scholar 

  25. Wu P, Liu Q, Li R, Wang J, Zhen X, Yue G, et al. Facile preparation of paclitaxel loaded silk fibroin nanoparticles for enhanced antitumor efficacy by locoregional drug delivery. ACS Appl Mater Interfaces. 2013;5(23):12638–45. https://doi.org/10.1021/am403992b.

    Article  CAS  PubMed  Google Scholar 

  26. Zhao Z, Li Y, Zhang Y. Preparation and characterization of paclitaxel loaded SF/PLLA-PEG-PLLA nanoparticles via solution-enhanced dispersion by supercritical CO2. J Nanomater. 2015;913254. https://doi.org/10.1155/2015/913254.

  27. Wu M, Yang W, Chen S, Yao J, Shao Z, Chen X. Size-controllable dual drug-loaded silk fibroin nanospheres through a facile formation process. J Mater Chem B. 2018;6:1179–86. https://doi.org/10.1039/C7TB03113K.

    Article  CAS  PubMed  Google Scholar 

  28. Pham DT, Saelim N, Tiyaboonchai W. Crosslinked fibroin nanoparticles using EDC or PEI for drug delivery: physicochemical properties, crystallinity and structure. J Mater Sci. 2018;53(20):14087–103. https://doi.org/10.1007/s10853-018-2635-3.

    Article  CAS  Google Scholar 

  29. Pham DT, Saelim N, Tiyaboonchai W. Design of experiments model for the optimization of silk fibroin based nanoparticles. Int J App Pharm. 2018;10(5):195–201. https://doi.org/10.22159/ijap.2018v10i5.28139.

    Article  CAS  Google Scholar 

  30. Liggins RT, Hunter WL, Burt HM. Solid-state characterization of paclitaxel. J Pharm Sci. 1997;86(12):1458–63. https://doi.org/10.1021/js9605226.

    Article  CAS  PubMed  Google Scholar 

  31. Pham DT, Saelim N, Tiyaboonchai W. Alpha mangostin loaded crosslinked silk fibroin-based nanoparticles for cancer chemotherapy. Colloids Surf B: Biointerfaces. 2019;181:705–13. https://doi.org/10.1016/j.colsurfb.2019.06.011.

    Article  CAS  PubMed  Google Scholar 

  32. Israelachvili J. Intermolecular & Surface Forces. 3rd ed. Cambridge: London Academic Press; 1985.

    Google Scholar 

  33. Macpherson SA, Webber GB, Moreno-Atanasio R. Aggregation of nanoparticles in high ionic strength suspensions: effect of Hamaker constant and particle concentration. Adv Powder Technol. 2012;23(4):478–84. https://doi.org/10.1016/j.apt.2012.04.008.

    Article  CAS  Google Scholar 

  34. Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci U S A. 1997;94(8):4028–33. https://doi.org/10.1073/pnas.94.8.4028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hoskins J, DeHerdt SV, Moore RE, Bumol TF. The development and characterization of Vinca alkaloid-resistant Caco-2 human colorectal cell lines expressing mdr-1. Int J Cancer. 1993;53(4):680–8. https://doi.org/10.1002/ijc.2910530426.

    Article  CAS  PubMed  Google Scholar 

  36. Yamada H, Igarashi Y, Takasu Y, Saito H, Tsubouchi K. Identification of fibroin-derived peptides enhancing the proliferation of cultured human skin fibroblasts. Biomaterials. 2004;25(3):467–72. https://doi.org/10.1016/S0142-9612(03)00540-4.

    Article  CAS  PubMed  Google Scholar 

  37. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10(1):9–22. https://doi.org/10.1038/nrc2748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bray LJ, Suzuki S, Harkin DG, Chirila TV. Incorporation of exogenous RGD peptide and inter-species blending as strategies for enhancing human corneal limbar epithelial cell growth on Bombyx mori silk fibroin membranes. J Funct Biomater. 2013;4(2):74–88. https://doi.org/10.3390/jfb4020074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Duy Toan Pham thanks Naresuan University ASEAN Scholarship, the RGJ Ph.D. Grant, the Boosting Research Potential for NU Students (Batch 4) Fellowship, and the Naresuan University Scholarship for Oral Presentation for funding his doctoral study. We also want to thank the staff of the Faculty of Pharmaceutical Sciences, Naresuan University, for their kind guidance. Thank you, mom, dad, and Phung for everything.

Funding

This study received financial support from the Thailand Research Fund (TRF) under the Royal Golden Jubilee (RGJ) Ph.D. Grant No. PHD/0234/2560 RGJ and the Naresuan University Grant No. R2561B009.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Naresuan University, 99 Moo 9, Amphoe Muang, Phitsanulok, 65000, Thailand

    Duy Toan Pham, Nuttawut Saelim & Waree Tiyaboonchai

  2. The Center of Excellence for Innovation in Chemistry (PERCH-CIC), Commission on Higher Education, Ministry of Education, Bangkok, Thailand

    Waree Tiyaboonchai

  3. The Center of Excellence in Medical Biotechnology, Naresuan University, Phitsanulok, 65000, Thailand

    Waree Tiyaboonchai

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  1. Duy Toan Pham
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Correspondence to Waree Tiyaboonchai.

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Highlights

- Novel paclitaxel loaded EDC-crosslinked silk fibroin nanoparticles were developed.

- Particle properties were controlled favorably.

- All formulations were non-toxic to the red blood cells and retained paclitaxel action on Caco-2 and MCF-7 cancer cell lines.

- In Caco-2 cells, the particles increased paclitaxel potency up to 10-fold.

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Pham, D.T., Saelim, N. & Tiyaboonchai, W. Paclitaxel loaded EDC-crosslinked fibroin nanoparticles: a potential approach for colon cancer treatment. Drug Deliv. and Transl. Res. 10, 413–424 (2020). https://doi.org/10.1007/s13346-019-00682-7

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