Preparation and in-vitro evaluation of PU- PCL films containing doxorubicin and ezetimibe on the prostate cancer cell line PC3

Document Type : Original Research Article

Authors

1 Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, Iran

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

4 Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

10.22034/nmrj.2024.01.003

Abstract

One of the most potentially hazardous diseases, prostate cancer has a high morbidity and mortality rate. Polymeric matrix drug-eluting implants have become widely employed, and modeling their behavior is becoming more and more prominent. It is always difficult to achieve effective drug delivery and release of it into specific tumor sites. One of the most significant purposes of this investigation, is the enhancement of the anticancer effects of prostate cancer treatment by co-delivering anticancer multi-drugs with PU-PCL films. The films were recognized utilizing SEM  (scanning electron microscopy) while the material was being characterized. In addition, the MTT assay and flow cytometry (Annexin V/PI staining) have been employed to assess cell viability at various times. A dialysis approach was used to investigate the drug release characteristics of DOX and Ezetimibe in films in vitro for 5 days. To optimize pharmacokinetic profiles and reduce systemic toxicity induced by drugs, we loaded polymeric PU-PCL films with ezetimibe (EZ) and doxorubicin (DOX). Co-delivery of EZ and DOX via film-carrier demonstrated improved anticancer effects when compared to free drug delivery. The co-delivery of DOX and EZ drugs by PU-PCL films improved anticancer effects while reducing systemic toxicity, suggesting clinical usage of drug-resistant prostate cancer therapy.

Keywords

Main Subjects

References

  1. F.Bray, J.Ferlay, I.Soerjomataram, R.L.Siegel, L.A.Torre, A.Jemal, Global cancer statistics 2018, GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA, Cancer J Clin, 2018, 68, 394-424. https://doi.org/10.3322/caac.21492
  2. G.K, Panigrahi, P.P. Praharaj, H. Kittaka, A.R. Mridha, O.M. Black, R. Singh, R. Mercer, A. Van Bokhoven, K.C. Torkko, C. Agarwal, Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients. Cancer Med, 2019, 8, 1110-1123. https://doi.org/10.1002/cam4.1885
  3. J. Ferlay, M. Ervik, F. Lam, M. Colombet, L. Mery, M. Piñeros, A. Znaor, I. Soerjomataram, F. Bray, Global cancer observatory: cancer today. Lyon, France: international agency for research on cancer, 2018, 1-6.
  4. E.D. Crawford, Epidemiology of prostate cancer. Urology, 2003, 62, 3-12. https://doi.org/10.1016/j.urology.2003.10.013
  5. J.M. Chan, P.H. Gann, E.L. Giovannucci, Role of diet in prostate cancer development and progression. J Clin Oncol, 2005, 23, 8152-8160. https://doi.org/10.1200/JCO.2005.03.1492
  6. E, Giovannucci, E.B. Rimm, G.A. Colditz, M.J. Stampfer, A. Ascherio, C.C. Chute, W.C. Willett, A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst, 1993, 85, 1571-1579. https://doi.org/10.1093/jnci/85.19.1571
  7. L.N. Kolonel, A.M. Nomura, R.V. Cooney, Dietary fat and prostate cancer: current status. J Natl Cancer Inst, 1999, 91, 414-428. https://doi.org/10.1093/jnci/91.5.414
  8. M.S. Willis, F.H. Wians Jr, The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances. Clin Chim Acta, 2003, 330(1-2), 57-83. https://doi.org/10.1016/S0009-8981(03)00048-2
  9. N.R. Perdana, C.A. Mochtar, R. Umbas, A.R.A. Hamid, The risk factors of prostate cancer and its prevention: a literature review. Acta Med Indones, 2017, 48, 228-238.
  10. W. Zhang, X. Zheng, S. Shen, X. Wang, Doxorubicin-loaded magnetic nanoparticle clusters for chemo-photothermal treatment of the prostate cancer cell line PC3. Biochem Biophys Res Commun, 2015, 466, 278-282. https://doi.org/10.1016/j.bbrc.2015.09.036
  11. S.Y. Madani, N. Naderi, O. Dissanayake, A. Tan, A.M. Seifalian, A new era of cancer treatment: carbon nanotubes as drug delivery tools. Int J Nanomedicine, 2011, 6, 2963. https://doi.org/10.2147/IJN.S16923
  12. X. Yao, P. Huang, Z. Nie, Cyclodextrin-based polymer materials: from controlled synthesis to applications, Prog. Polym Sci, 2019, 93, 1-35. https://doi.org/10.1016/j.progpolymsci.2019.03.004
  13. T.K. Dash, V.B. Konkimalla, Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A review. J Control Release, 2012, 158, 15-33. https://doi.org/10.1016/j.jconrel.2011.09.064
  14. A. Azadi, M. Hamidi, M.R. Rouini, Methotrexate-loaded chitosan nanogels as 'Trojan Horses' for drug delivery to brain: preparation and in vitro/in vivo characterization. Int J Biol Macromol, 2013, 62, 523-530. https://doi.org/10.1016/j.ijbiomac.2013.10.004
  15. J.H. Lee, K.J. Chen, S.H. Noh, M.A. Garcia, H. Wang, W.Y. Lin, H. Jeong, B.J. Kong, D.B. Stout, J. Cheon, On demand drug release system for in vivo cancer treatment through self‐assembled magnetic nanoparticles. Angew Chem Int Ed, 2013, 125, 4480-4484. https://doi.org/10.1002/ange.201207721
  16. X. Yang, D. He, X. He, K. Wang, Z. Zou, X. Li, H. Shi, J. Luo, X. Yang, Glutathione Mediated Degradation of Surface‐Capped MnO2 for Drug Release from Mesoporous Silica Nanoparticles to Cancer Cells. Part Part Syst Charact, 2015, 32, 205-212. https://doi.org/10.1002/ppsc.201400092
  17. D. Ho, J.W. Leong, R.C. Crew, M. Norret, M.J. House, P.J. Mark, B.J. Waddell, K.S. Iyer, J.A. Keelan, Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation. Sci Rep, 2017, 7, 1-11. https://doi.org/10.1038/s41598-017-03128-7
  18. A. Schroeder, D.A. Heller, M.M. Winslow, J.E. Dahlman, G.W. Pratt, R. Langer, T. Jacks, D.G. Anderson, Treating metastatic cancer with nanotechnology. Nat Rev Cancer 2012, 12, 39-50. https://doi.org/10.1038/nrc3180
  19. R. Kumar, A. Kulkarni, J. Nabulsi, D.K. Nagesha, R. Cormack, M.G. Makrigiorgos, S. Sridhar, Facile synthesis of PEGylated PLGA nanoparticles encapsulating doxorubicin and its in vitro evaluation as potent drug delivery vehicle. Drug Deliv Transl, 2013, 3, 299-308. https://doi.org/10.1007/s13346-012-0124-9
  20. A.D. Salaam, P.T. Hwang, A. Poonawalla, H.N. Green, H.w. Jun, D. Dean. Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer. Nanotechnology, 2014, 25, 425103. https://doi.org/10.1088/0957-4484/25/42/425103
  21. H.J. Kwon, S. Park, Local delivery of antiproliferative agents via stents. Polymers, 2014 6, 755-775. https://doi.org/10.3390/polym6030755
  22. M. Shaikh, G. Kichenadasse, N.R. Choudhury, R. Butler, S. Garg, Non-vascular drug eluting stents as localized controlled drug delivery platform: preclinical and clinical experience. J Control Release, 2013, 172, 105-117. https://doi.org/10.1016/j.jconrel.2013.08.010
  23. M. Arafat, P. Fouladian, A. Blencowe, H. Albrecht, Y. Song, S. Garg, Drug-eluting non-vascular stents for localised drug targeting in obstructive gastrointestinal cancers. J Control Release, 2019, 308, 209-231. https://doi.org/10.1016/j.jconrel.2019.07.001
  24. S. Baudis, F. Nehl, S.C. Ligon, A. Nigisch, H. Bergmeister, D. Bernhard, J. Stampfl, R. Liska, Elastomeric degradable biomaterials by photopolymerization-based CAD-CAM for vascular tissue engineering. Biomed Mater, 2011, 6, 055003. https://doi.org/10.1088/1748-6041/6/5/055003
  25. J.Y. Cherng, T.Y. Hou, M.F. Shih, H. Talsma, W.E. Hennink. Polyurethane-based drug delivery systems. Int J Pharm, 2013, 450, 145-162. https://doi.org/10.1016/j.ijpharm.2013.04.063
  26. C. Akduman, I. Özgüney, E.P.A. Kumbasar, Preparation and characterization of naproxen-loaded electrospun thermoplastic polyurethane nanofibers as a drug delivery system. Mater Sci Eng C, 2016, 64, 383-390. https://doi.org/10.1016/j.msec.2016.04.005
  27. M.B. Lowinger, S.E. Barrett, F. Zhang, R.O. Williams, Sustained release drug delivery applications of polyurethanes. Pharmaceutics, 2018, 10, 55. https://doi.org/10.3390/pharmaceutics10020055
  28. K.M. Gupta, S.M. Pearce, A.E. Poursaid, H.A. Aliyar, P.A. Tresco, M.A. Mitchnik, P.F. Kiser, Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1. J Pharm Sci, 2008, 97, 4228-4239. https://doi.org/10.1002/jps.21331
  29. L.P. Bucky, H.P. Ehrlich, S. Sohoni, Jr. J.W. May, The capsule quality of saline-filled smooth silicone, textured silicone, and polyurethane implants in rabbits: a long-term study. Plast Reconstr Surg, 1994, 93,1123-1131; discussion 1132. https://doi.org/10.1097/00006534-199405000-00002
  30. S. Sommer, A. Ekin, D.C. Webster, S.J Stafslien, J. Daniels, L.J. VanderWal, S.E. Thompson, M.E. Callow, J.A. Callow, A preliminary study on the properties and fouling-release performance of siloxane-polyurethane coatings prepared from poly (dimethylsiloxane)(PDMS) macromers. Biofouling, 2010, 26,961-972. https://doi.org/10.1080/08927014.2010.531272
  31. T.K. Dash, V.B. Konkimalla, Polymeric modification and its implication in drug delivery: poly-ε-caprolactone (PCL) as a model polymer. Mol Pharm, 2012, 9, 2365-2379. https://doi.org/10.1021/mp3001952
  32. A. Shababdoust , M. Zandi, M. Ehsani, P. Shokrollahi, R. Foudazi, Controlled curcumin release from nanofibers based on amphiphilic-block segmented polyurethanes. Int J Pharm, 2020, 575, 118947. https://doi.org/10.1016/j.ijpharm.2019.118947
  33. S. Gao, A. Zhou, B. Cao, J. Wang, F. Li, G. Tang, Z. Jiang, A. Yang, R. Xiong, J. Lei, A tunable temperature-responsive and tough platform for controlled drug delivery, 2021, New J Chem. https://doi.org/10.1039/D1NJ01356D
  34. M. Irani, G.M.M. Sadeghi, I. Haririan, A novel biocompatible drug delivery system of chitosan/temozolomide nanoparticles loaded PCL-PU nanofibers for sustained delivery of temozolomide. Int J Biol, 2017, 97, 744-751. https://doi.org/10.1016/j.ijbiomac.2017.01.073
  35. M. Shahzamani, N.G. Ebrahimi, Effect of Solvent on the Properties of TPU (PCL)/PCL Blends Prepared by Solution Method.
  36. C.P. Teng, K.Y. Mya, K.Y. Win, C.C. Yeo, M. Low, C. He, M.Y. Han, Star-shaped polyhedral oligomeric silsesquioxane-polycaprolactone-polyurethane as biomaterials for tissue engineering application. NPG Asia Mater, 2014, 6, e142-e142. https://doi.org/10.1038/am.2014.102
  37. S. De Koker, R. Hoogenboom, B.G. De Geest, Polymeric multilayer capsules for drug delivery. Chem Soc Rev, 2012, 41, 2867-2884. https://doi.org/10.1039/c2cs15296g
  38. T.L. Doane, C. Burda. The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy. Chem Soc Rev. 2012, 41, 2885-2911. https://doi.org/10.1039/c2cs15260f
  39. C.F. Thorn, C. Oshiro, S. Marsh, T. Hernandez-Boussard, H. McLeod, T.E. Klein, R.B. Altman, Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics, 2011, 21, 440. https://doi.org/10.1097/FPC.0b013e32833ffb56
  40. X. Xu, X. Chen, X. Wang, X. Jing, The release behavior of doxorubicin hydrochloride from medicated fibers prepared by emulsion-electrospinning. Eur. J. Pharm. Biopharm, 2008, 70(1), 165-170. https://doi.org/10.1016/j.ejpb.2008.03.010
  41. F. Yang, J. Xu, M. Fu, J. Ji, L. Chi, G. Zhai, Development of stimuli-responsive intelligent polymer micelles for the delivery of doxorubicin. J. Drug Target, 2020, 28(10), 993-1011. https://doi.org/10.1080/1061186X.2020.1766474
  42. S .Davaran, et al, Physicochemical characteristics of Fe 3 O 4 magnetic nanocomposites based on poly (N-isopropylacrylamide) for anti-cancer drug delivery. Asian Pacific Journal of Cancer Prevention, 2014. 15(1), p. 49-54. https://doi.org/10.7314/APJCP.2014.15.1.49
  43. C. Dhand, N. Dwivedi, H. Sriram, S. Bairagi, D. Rana, R. Lakshminarayanan, M. Ramalingam, S. Ramakrishna, Nanofiber composites in drug delivery. In: Nanofiber Composites for Biomedical Applications. Elsevier, 2017, 199-223. https://doi.org/10.1016/B978-0-08-100173-8.00008-9
  44. B. Dhandayuthapani, D. Sakthi kumar. Biomaterials for biomedical applications. Biomedical Applications of Polymeric Materials and Composites, 2016, 1-20. https://doi.org/10.1002/9783527690916.ch1
  45. P.X. Ma, J.W. Choi, Biodegradable polymer scaffolds with well-defined interconnected spherical pore network. Tissue Eng, 2001, 7, 23-33. https://doi.org/10.1089/107632701300003269
  46. S. Zhang, Z.T. Li, M. Liu, J.R. Wang, M.Q. Xu, Z.Y. Li, X.C. Duan, Y.L. Hao, X.C. Zheng, H. Li, Anti-tumour activity of low molecular weight heparin doxorubicin nanoparticles for histone H1 high-expressive prostate cancer PC-3M cells. J Control Release, 2019, 295, 102-117. https://doi.org/10.1016/j.jconrel.2018.12.034
  47. W. Zheng, M. Li, Y. Lin, X. Zhan, Encapsulation of verapamil and doxorubicin by MPEG-PLA to reverse drug resistance in ovarian cancer. Biomed Pharmacother, 2018, 108,565-573. https://doi.org/10.1016/j.biopha.2018.09.039
  48. M. Norouzi, V. Yathindranath, J.A. Thliveris, B.M. Kopec, T.J. Siahaan, D.W. Miller, Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: A combinational approach for enhanced delivery of nanoparticles. Sci Rep, 2020, 10, 1-18. https://doi.org/10.1038/s41598-020-68017-y
  49. E. Tsakalozou, A.M. Eckman, Y. Bae, Combination effects of docetaxel and doxorubicin in hormone-refractory prostate cancer cells, 2012, Biochem Res Int 2012. https://doi.org/10.1155/2012/832059
  50. R.Mohammadi Abandansari, H. Parsian, F. Kazerouni, R. Porbagher, E Zabihi, A. Rahimipour, Effect of simultaneous treatment with royal jelly and doxorubicin on the survival of the prostate cancer cell line (pc3), an in vitro study, 2018, Int J Cancer Manag 11. https://doi.org/10.5812/ijcm.13780
  51. F. Almutairi, T.C. Peterson, M. Molinari, M.J. Walsh, I. Alwayn, K.M. Peltekian, Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia. Liver Transplant, 2009, 15, 504-508. https://doi.org/10.1002/lt.21710
  52. L. Zhuang, J. Kim, R.M. Adam, K.R. Solomon, M.R. Freeman, Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Investig, 2005, 115, 959-968.
  53. K.R. Solomon, K. Pelton, K. Boucher, J. Joo, C. Tully, D. Zurakowski, C.P. Schaffner, J. Kim, M.R. Freeman, Ezetimibe is an inhibitor of tumor angiogenesis. Am J Pathol, 2009, 174, 1017-1026. https://doi.org/10.2353/ajpath.2009.080551

54. C. Pisani, M. Ramella, R. Boldorini, G. Loi, M. Billia, F. Boccafoschi, A. Volpe, M. Krengli, Apoptotic and predictive factors by Bax, Caspases 3/9, Bcl-2, p53 and Ki-67 in prostate cancer after 12 Gy single-dose, Scientific reports, 10 (2020) 7050. https://doi.org/10.1038/s41598-020-64062-9

55. R. Habibey, M. Ajami, S.A. Ebrahimi, A. Hesami, S. Babakoohi, H. Pazoki-Toroudi, Nitric oxide and renal protection in morphine-dependent rats, Free Radical Biology and Medicine, 49 (2010) 1109-1118. https://doi.org/10.1016/j.freeradbiomed.2010.06.024

56. M. Ajami, S. Eghtesadi, J.M. Razaz, N. Kalantari, R. Habibey, M.A. Nilforoushzadeh, M. Zarrindast, H. Pazoki-Toroudi, Expression of Bcl-2 and Bax after hippocampal ischemia in DHA+ EPA treated rats, Neurological Sciences, 32 (2011) 811-818. https://doi.org/10.1007/s10072-011-0621-5

57. G. Javedan, F. Shidfar, S.H. Davoodi, M. Ajami, F. Gorjipour, A. Sureda, S.M. Nabavi, M. Daglia, H. Pazoki‐Toroudi, Conjugated linoleic acid rat pretreatment reduces renal damage in ischemia/reperfusion injury: Unraveling antiapoptotic mechanisms and regulation of phosphorylated mammalian target of rapamycin, Molecular nutrition & food research, 60 (2016) 2665-2677. https://doi.org/10.1002/mnfr.201600112

58. H. Ghaznavi, S. Mehrzadi, B. Dormanesh, S.M.T.H. Tabatabaei, H. Vahedi, A. Hosseinzadeh, H. Pazoki-Toroudi, A. Rashidian, Comparison of the protective effects of melatonin and silymarin against gentamicin-induced nephrotoxicity in rats, Journal of evidence-based complementary & alternative medicine, 21 (2016) NP49-NP55. https://doi.org/10.1177/2156587215621672

59. F.Z. Mehrjerdi, N. Aboutaleb, H. Pazoki-Toroudi, M. Soleimani, M. Ajami, M. Khaksari, F. Safari, R. Habibey, The protective effect of remote renal preconditioning against hippocampal ischemia reperfusion injury: role of KATP channels, Journal of molecular neuroscience, 57 (2015) 554-560. https://doi.org/10.1007/s12031-015-0636-0

Nanomedicine Research Journal
Volume 9, Issue 1
March 2024
Pages 20-29

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