Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in HER-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer

Author(s): Erfaneh Ghassami, Jaleh Varshosaz*, Mohsen Minaiyan, Mehrab Nasirikenari, Seyed M. Hoseini.

Journal Name: Recent Patents on Nanotechnology

Volume 13 , Issue 1 , 2019

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Abstract:

Background: Docetaxel is a notably efficient anticancer drug administered for several types of malignancies including ovarian cancer. However, various side effects caused either by the nonspecific distribution of the active ingredient or by high contents of Tween 80 and ethanol in the currently marketed formulations, could even deprive the patients of the treatment.

Objectives: In the current study, a novel targeted delivery system composed of Ecoflex® polymeric nanoparticles loaded with docetaxel and equipped with HER-2 specific aptamer molecules was evaluated regarding blood and tissue toxicity, and biodistribution.

Method: The tumor-bearing nude mice, achieved by subcutaneous injection of SKOV-3 cells, were divided into four groups treated with normal saline, Taxotere®, targeted docetaxel nanoparticles, and non-targeted docetaxel nanoparticles. Few patents were alos cied in the article.

Results: According to the results of hematologic evaluations, almost all hematologic parameters were in normal range with no significant difference among the four groups. Histopathological studies revealed that treatment with targeted nanoparticles caused a remarkable reduction in mitosis in tumor sections and overall reduced organ toxicity compared with Taxotere®. The only exception was spleen in which more damage was caused by the nanoparticles. The results of the biodistribution study were also in accordance with pathological assessments, with significantly lower drug concentration in non-tumor tissues, except for spleen, when targeted nanoparticles were used compared with Taxotere®.

Conclusion: These results could evidence the efficiency of the targeted delivery system in concentrating the drug cargo mostly in its site of action leading to the elimination of its adverse effects caused by exposure of other tissues to the cytotoxic agent.

Keywords: Aptamer, biodistribution, docetaxel, ecoflex, nanoparticles, organ toxicity.

[1]
Engels FK, Mathot RA, Verweij J. Alternative drug formulations of docetaxel: A review. Anticancer Drugs 2007; 18(2): 95-103.
[2]
Wang L, Liu Z, Liu D, Liu C, Juan Z, Zhang N. Docetaxel-loaded-lipid-based-nanosuspensions (DTX-LNS): Preparation, pharmacokinetics, tissue distribution and antitumor activity. Int J Pharm 2011; 413(1-2): 194-201.
[3]
Liu Q, Li R, Zhu Z, et al. Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles. Int J Pharm 2012; 430(1-2): 350-8.
[4]
Trudeau ME, Eisenhauer EA, Higgins BP, et al. Docetaxel in patients with metastatic breast cancer: A phase II study of the National Cancer Institute of Canada - Clinical Trials Group. J Clin Oncol 1996; 14(2): 422-8.
[5]
Piccart MJ, Gore M, Ten Bokkel Huinink W, et al. Docetaxel: An active new drug for treatment of advanced epithelial ovarian cancer. J Natl Cancer Inst 1995; 87(9): 676-81.
[6]
Bruno R, Hille D, Riva A, et al. Population pharmacokinetics/ pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 1998; 16(1): 187-96.
[7]
Ardavanis A, Tryfonopoulos D, Yiotis I, et al. Non-allergic nature of docetaxel-induced acute hypersensitivity reactions. Anticancer Drugs 2004; 15(6): 581-5.
[8]
Palepu NR, Bulusu BT. Solubilized formulation of docetaxel without tween 80. US Patent 20080319048A1, 2008
[9]
Shelley M, Harrison C, Coles B, et al. Chemotherapy for hormone-refractory prostate cancer. Cochrane Database Syst Rev 2006; 18(4): CD005247.
[10]
Van Poppel H. Recent docetaxel studies establish a new standard of care in hormone refractory prostate cancer. Can J Urol 2005; 12: 81-5.
[11]
Baker J, Ajani J, Scotté F, et al. Docetaxel-related side effects and their management. Eur J Oncol Nurs 2008; 12(3): 253-68.
[12]
Esmaeli B, Valero V, Ahmadi MA, Booser D. Canalicular stenosis secondary to docetaxel (taxotere): A newly recognized side effect. Ophthalmology 2001; 108(5): 994-5.
[13]
Aapro M. Docetaxel versus doxorubicin in patients with metastatic breast cancer who have failed alkylating chemotherapy: A preliminary report of the randomized phase III trial. 303 Study Group. Semin Oncol 1998; 25: 7-11.
[14]
Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: The M77001 study group. J Clin Oncol 2005; 23(19): 4265-74.
[15]
Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 non-small cell lung cancer study group. J Clin Oncol 2000; 18(12): 2354-62.
[16]
Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003; 21(16): 3016-24.
[17]
Remenar E, Van Herpen C, Lluch JG, et al. A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable Squamous Cell Carcinoma of the Head And Neck (SCCHN). J Clin Oncol 2006; 24(18): 5516.
[18]
Chan S. Docetaxel vs. doxorubicin in metastatic breast cancer resistant to alkylating chemotherapy. Oncology (Williston Park) 1997; 11: 19-24.
[19]
Shen G, Yu H, Bian G, et al. Genistein inhibits the proliferation of human HER2-positive cancer cells by downregulating HER2 receptor. Funct Food Health Dis 2013; 3(7): 291-9.
[20]
Vogel CL, Bellet RE. Use of docetaxel for treating cancers, US Patent 6333348B1, 2001
[21]
Mahapatro A, Singh DK. Biodegradable nanoparticles are excellentvehicle for site directed in vivo delivery of drugs and vaccines. J Nanobiotechnology 2011; 9: 55.
[22]
Vasir JK, Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev 2007; 59(8): 718-28.
[23]
Liversidge G, Jenkins S, Liversidge E. . Nanoparticulate formulations of docetaxel and analogues thereof. US Patent 20060188566A1, 2006
[24]
Parijat P, Harish D. Recent patents on polymeric nanoparticles for cancer therapy. Recent Pat Nanotechnol 2018; 12(2): 155-69.
[25]
Labhasetwar V, Song C, Levy RJ. Nanoparticle drug delivery system for restenosis. Adv Drug Deliv Rev 1997; 24(1): 63-85.
[26]
Li H, Zhang Q, Sun X. XU Y, Huang W, Li A. Method for synthesizing poly(butylene adipate-co-terephthalate). US Patent 9896539B2, 2018
[27]
Khemani K, Andersen PJ, Hodson SK, Schmidt H. . Biodegradable polymer films and sheets suitable for use as laminate coatings as well as wraps and other packaging materials. US Patent 6573340B1, 2003.
[28]
Youli X, Jun J, Yuyu L. PBAT (polybutyrate adipate terephthalate) Fully-biodegradable film composition and preparation method thereof. Chinese Patent 107189365A, 2017
[29]
Varshosaz J, Riahi S, Ghassami E, Jahanian-Najafabadi A. Transferrin-targeted poly(butylene adipate)/terephthalate nanoparticles for targeted delivery of 5-fluorouracil in HT29 colorectal cancer cell line. J Bioact Compat Polym 2017; 32(5): 503-27.
[30]
Bodor N. Redox drug delivery systems for targeting drugs to the brain. Ann N Y Acad Sci 1987; 507: 289-306.
[31]
Chames P, Van Regenmortel M, Weiss E, Baty D. Therapeutic antibodies: Successes, limitations and hopes for the future. Br J Pharmacol 2009; 157(2): 220-33.
[32]
O’Sullivan CK. Aptasensors - the future of biosensing. Anal Bioanal Chem 2002; 372(1): 44-8.
[33]
Mills JK, Needham D. Targeted drug delivery. J Expert Opin Ther Pat 1999; 9: 1499-513.
[34]
Meyer C, Hahn U, Rentmeister A. Cell-specific aptamers as emerging therapeutics. J Nucleic Acids 2011; 2011: 904750.
[35]
Mairal T, Özalp VC, Sánchez PL, Mir M, Katakis I, O’Sullivan CK. Aptamers: Molecular tools for analytical applications. Anal Bioanal Chem 2008; 390: 989-1007.
[36]
Murphy MB, Fuller ST, Richardson PM, Doyle SA. An improved method for the in vitro evolution of aptamers and applications in protein detection and purification. Nucleic Acids Res 2003; 31(18): e110.
[37]
Varshosaz J, Ghassami E, Noorbakhsh A, et al. Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice. Drug Dev Ind Pharm 2018; 44(6): 1012-22.
[38]
Rutkowski S, Si T, Gai M, Frueh J, He Q. Hydrodynamic electrospray ionization jetting of calcium alginate particles: Effect of spray-mode, spraying distance and concentration. RSC Advances 2018; 8: 24243.
[39]
Collery P, Mohsen A, Kermagoret A, et al. Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer. Invest New Drugs 2015; 33(4): 848-60.
[40]
Taymouri S, Varshosaz V, Hassanzadeh F, et al. Pharmacokinetics, organ toxicity and antitumor activity of docetaxel loaded in folate targeted cholesterol based micelles. Curr Drug Deliv 2016; 13(4): 545-56.
[41]
Cardiff RD, Miller CH, Munn RJ. Manual hematoxylin and eosin stainy of mouse tissues section. Cold Spring Harb Protoc 2014; 2014(6): 655-8.
[42]
Bruey JM, Maher A. Cancer diagnosis using ki-67. US Patent 20100120080A1, 2010
[43]
Cervin C, Tinzl M, Johnsson M, et al. Properties and effects of a novel liquid crystal nanoparticle formulation of docetaxel in a prostate cancer mouse model. Eur J Pharm Sci 2010; 41(2): 369-75.
[44]
Feng SX, Guan Q, Chen T, et al. In vitro activities of 3-hydroxy-1,5,6-trimethoxy-2-methyl-9,10-anthraquinone against non-small cell lung carcinoma. Arch Pharm Res 2012; 35: 1251-8.
[45]
Ernsting MJ, Tang WL, MacCallum NW, et al. Preclinical pharmacokinetic, biodistribution, and anti-cancer efficacy studies of a docetaxel-carboxymethylcellulose nanoparticle in mouse models. Biomaterials 2012; 33(5): 1445-54.
[46]
Miki Y, Yoshimoto K, Isomura A. Methods and kits for predicting the side effects of docetaxel therapyJapanese Patent 5015547B2, 2012
[47]
O’Connell KE, Mikkola AM, Stepanek AM, et al. Practical murine hematopathology: A comparative review and implications for research. Comp Med 2015; 65(2): 96-113.
[48]
Cataldi M, Vigliotti C, Mosca T, et al. Emerging Role of the Spleen in the Pharmacokinetics of Monoclonal Antibodies, Nanoparticles and Exosomes. Int J Mol Sci 2017; 18(6): E1249.
[49]
Frank GU. Nanoparticle delivery system and components thereof. US Patent 20140005379A1, 2014
[50]
Gokhale PC, Radhakrishnan B, Husain SR, et al. An improved method of encapsulation of doxorubicin in liposomes: Pharmacological, toxicological and therapeutic evaluation. Br J Cancer 1996; 74(1): 43-8.
[51]
Zhao L, Wei YM, Zhong XD, et al. PK and tissue distribution of docetaxel in rabbits after i.v. administration of liposomal and injectable formulations. J Pharm Biomed Anal 2009; 49(4): 989-96.
[52]
He W, Frueh J, Wu Z, He Q. Leucocyte membrane-coated janus microcapsules for enhanced photothermal cancer treatment. Langmuir 2016; 32: 3637.
[53]
Gai M, Frueh J, Kudryavtseva VL, Yashchenok AM, Sukhorukov GB. Polylactic acid sealed polyelectrolyte multilayer microchambers for entrapment of salts and small hydrophilic molecules precipitates. Appl Mater Interfaces 2017; 9: 16536.
[54]
Li W, Gai M, Rutkowski S, et al. Automated device for layer-by-layer coating of dispersed superparamagnetic nanoparticle templates. Colloid J 2018; 80: 648-59.


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Article Details

VOLUME: 13
ISSUE: 1
Year: 2019
Page: [49 - 58]
Pages: 10
DOI: 10.2174/1872210513666181128162403
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