Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Development and Evaluation of Biotin Functionalized Fullerenes for the Delivery of Irinotecan to Colon Tumors

Author(s): Shikha Dhiman, Amardeep Kaur, Girdhari L. Gupta and Manu Sharma*

Volume 20, Issue 7, 2023

Published on: 01 August, 2022

Page: [978 - 991] Pages: 14

DOI: 10.2174/1567201819666220516153010

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy.

Objective: The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex.

Methods: Fullerene (C60) has been observed as a potential drug delivery agent and the aminefunctionalized C60-NH2 was synthesized by functionalizing ethylenediamine on the surface of C60. The PEI functionalized C60 was further synthesized by polymerization of aziridine on the surface of C60- NH2. Biotin was attached by an amide linkage to C60-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C60-PEI-Biotin/IRI). The C60-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan.

Results: The results showed that C60-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan.

Conclusion: It is hypothesized that the conjugate (C60-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.

Keywords: Irinotecan, fullerenes, biotin, nanoparticles, drug delivery, colon cancer, cell membrane.

« Previous
Graphical Abstract

[1]
Langer, R. Drug delivery and targeting. Nature, 1998, 392(6679)(Suppl.), 5-10.
[PMID: 9579855]
[2]
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), 6387-6392.
[PMID: 2946403]
[3]
Moghimi, S.M.; Hunter, A.C.; Murray, J.C. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol. Rev., 2001, 53(2), 283-318.
[PMID: 11356986]
[4]
Moghimi, S.M.; Hunter, A.C.; Murray, J.C. Nanomedicine: Current status and future prospects. FASEB J., 2005, 19(3), 311-330.
[http://dx.doi.org/10.1096/fj.04-2747rev] [PMID: 15746175]
[5]
Youns, M.; Hoheisel, J.D.; Efferth, T. Therapeutic and diagnostic applications of nanoparticles. Curr. Drug Targets, 2011, 12(3), 357-365.
[http://dx.doi.org/10.2174/138945011794815257] [PMID: 20955146]
[6]
Sánchez, L.; Otero, R.; Gallego, J.M.; Miranda, R.; Martín, N. Ordering fullerenes at the nanometer scale on solid surfaces. Chem. Rev., 2009, 109(5), 2081-2091.
[http://dx.doi.org/10.1021/cr800441b] [PMID: 19253947]
[7]
Nosik, D.N.; Lialina, I.K.; Kalnina, L.B.; Lobach, O.A.; Chataeva, M.S.; Rasnetsov, L.D. The antiretroviral agent Fullevir. Vopr. Virusol., 2009, 54(5), 41-43.
[PMID: 19882903]
[8]
Lai, H.S.; Chen, W.J.; Chiang, L.Y. Free radical scavenging activity of fullerenol on the ischemia-reperfusion intestine in dogs. World J. Surg., 2000, 24(4), 450-454.
[http://dx.doi.org/10.1007/s002689910071] [PMID: 10706918]
[9]
Nakamura, S.; Mashino, T. Water-soluble fullerene derivatives for drug discovery. J. Nippon Med. Sch., 2012, 79(4), 248-254.
[http://dx.doi.org/10.1272/jnms.79.248] [PMID: 22976602]
[10]
Durdagi, S.; Mavromoustakos, T.; Chronakis, N.; Papadopoulos, M.G. Computational design of novel fullerene analogues as potential HIV-1 PR inhibitors: Analysis of the binding interactions between fullerene inhibitors and HIV-1 PR residues using 3D QSAR, molecular docking and molecular dynamics simulations. Bioorg. Med. Chem., 2008, 16(23), 9957-9974.
[http://dx.doi.org/10.1016/j.bmc.2008.10.039] [PMID: 18996019]
[11]
Horie, M.; Fukuhara, A.; Saito, Y.; Yoshida, Y.; Sato, H.; Ohi, H.; Obata, M.; Mikata, Y.; Yano, S.; Niki, E. Antioxidant action of sugar-pendant C60 fullerenes. Bioorg. Med. Chem. Lett., 2009, 19(20), 5902-5904.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.067] [PMID: 19736008]
[12]
Zhou, W.; Yuan, X.; Wilson, A.; Yang, L.; Mokotoff, M.; Pitt, B.; Li, S. Efficient intracellular delivery of oligonucleotides formulated in folate receptor-targeted lipid vesicles. Bioconjug. Chem., 2002, 13(6), 1220-1225.
[http://dx.doi.org/10.1021/bc025569z] [PMID: 12440856]
[13]
Ratnam, M.; Hao, H.; Zheng, X.; Wang, H.; Qi, H.; Lee, R.; Pan, X. Receptor induction and targeted drug delivery: A new antileukaemia strategy. Expert Opin. Biol. Ther., 2003, 3(4), 563-574.
[http://dx.doi.org/10.1517/14712598.3.4.563] [PMID: 12831362]
[14]
Yao, V.; Berkman, C.E.; Choi, J.K.; O’Keefe, D.S.; Bacich, D.J. Expression of Prostate-Specific Membrane Antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. Prostate, 2010, 70(3), 305-316.
[http://dx.doi.org/10.1002/pros.21065] [PMID: 19830782]
[15]
Petersen, L.F.; Brockton, N.T.; Bakkar, A.; Liu, S.; Wen, J.; Weljie, A.M.; Bismar, T.A. Elevated physiological levels of folic acid can increase in vitro growth and invasiveness of prostate cancer cells. BJU Int., 2012, 109(5), 788-795.
[http://dx.doi.org/10.1111/j.1464-410X.2011.10437.x] [PMID: 21771248]
[16]
Weitman, S.D.; Weinberg, A.G.; Coney, L.R.; Zurawski, V.R.; Jennings, D.S.; Kamen, B.A. Cellular localization of the folate receptor: Potential role in drug toxicity and folate homeostasis. Cancer Res., 1992, 52(23), 6708-6711.
[PMID: 1330299]
[17]
Shi, J.; Zhang, H.; Wang, L.; Li, L.; Wang, H.; Wang, Z.; Li, Z.; Chen, C.; Hou, L.; Zhang, C.; Zhang, Z. PEI-derivatized fullerene drug delivery using folate as a homing device targeting to tumor. Biomaterials, 2013, 34(1), 251-261.
[http://dx.doi.org/10.1016/j.biomaterials.2012.09.039] [PMID: 23069706]
[18]
Rao, B.M.; Chakraborty, A.; Srinivasu, M.K.; Devi, M.L.; Kumar, P.R.; Chandrasekhar, K.B.; Srinivasan, A.K.; Prasad, A.S.; Ramanatham, J. A stability-indicating HPLC assay method for docetaxel. J. Pharm. Biomed. Anal., 2006, 41(2), 676-681.
[http://dx.doi.org/10.1016/j.jpba.2006.01.011] [PMID: 16473490]
[19]
Lee, S.; Murthy, N. Targeted delivery of catalase and superoxide dismutase to macrophages using folate. Biochem. Biophys. Res. Commun., 2007, 360(1), 275-279.
[http://dx.doi.org/10.1016/j.bbrc.2007.06.054] [PMID: 17586472]
[20]
Moes, J.J.; Koolen, S.L.; Huitema, A.D.; Schellens, J.H.; Beijnen, J.H.; Nuijen, B. Pharmaceutical development and preliminary clinical testing of an oral solid dispersion formulation of docetaxel (ModraDoc001). Int. J. Pharm., 2011, 420(2), 244-250.
[http://dx.doi.org/10.1016/j.ijpharm.2011.08.041] [PMID: 21907780]
[21]
Isakovic, A.; Markovic, Z.; Todorovic-Markovic, B.; Nikolic, N.; Vranjes-Djuric, S.; Mirkovic, M.; Dramicanin, M.; Harhaji, L.; Raicevic, N.; Nikolic, Z.; Trajkovic, V. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol. Sci., 2006, 91(1), 173-183.
[http://dx.doi.org/10.1093/toxsci/kfj127] [PMID: 16476688]
[22]
Matsuoka, K.; Matsumura, S.; Akiyama, T.; Yamada, S. Shape control of fullerene microparticles by using ethylenediamine. Chem. Lett., 2008, 37(9), 932-933.
[http://dx.doi.org/10.1246/cl.2008.932]
[23]
Peer, D.; Karp, J.M.; Hong, S.; Farokhzad, O.C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol., 2007, 2(12), 751-760.
[http://dx.doi.org/10.1038/nnano.2007.387] [PMID: 18654426]
[24]
Mignano, C.; Faghri, P.D.; Huedo-Medina, T.; Cherniack, M.C. Psychological health, behavior, and bodyweight (PBBW) model: An evaluation of predictors of health behaviors and Body Mass Index (BMI). J. Workplace Behav. Health, 2016, 31(1), 37-56.
[http://dx.doi.org/10.1080/15555240.2015.1100518]
[25]
Bruggeman, A.R.; Kamal, A.H.; LeBlanc, T.W.; Ma, J.D.; Baracos, V.E.; Roeland, E. J. Cancer cachexia: Beyond weight loss. J. Oncol. Pract., 2016, 12(11), 1163-1171.
[http://dx.doi.org/10.1200/JOP.2016.016832] [PMID: 27858548]
[26]
Lerner, L.; Hayes, T.G.; Tao, N.; Krieger, B.; Feng, B.; Wu, Z.; Nicoletti, R.; Chiu, M.I.; Gyuris, J.; Garcia, J.M. Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients. J. Cachexia Sarcopenia Muscle, 2015, 6(4), 317-324.
[http://dx.doi.org/10.1002/jcsm.12033] [PMID: 26672741]
[27]
Arikawa, A.Y.; Kaufman, B.C.; Raatz, S.K.; Kurzer, M.S. Effects of a parallel-arm randomized controlled weight loss pilot study on biological and psychosocial parameters of overweight and obese breast cancer survivors. Pilot Feasibility Stud., 2017, 4(1), 17-29.
[http://dx.doi.org/10.1186/s40814-017-0160-9] [PMID: 28702218]
[28]
McIntosh, G.H.; Regester, G.O.; Le Leu, R.K.; Royle, P.J.; Smithers, G.W. Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in rats. J. Nutr., 1995, 125(4), 809-816.
[PMID: 7722681]
[29]
Argilés, J.M.; Stemmler, B.; López-Soriano, F.J.; Busquets, S. Nonmuscle tissues contribution to cancer cachexia. Mediators Inflamm., 2015, 2015182872
[http://dx.doi.org/10.1155/2015/182872] [PMID: 26523094]
[30]
Kumar, S.; Agnihotri, N. Piperlongumine, a piper alkaloid targets Ras/PI3K/Akt/mTOR signaling axis to inhibit tumor cell growth and proliferation in DMH/DSS induced experimental colon cancer. Biomed. Pharmacother., 2019, 109, 1462-1477.
[http://dx.doi.org/10.1016/j.biopha.2018.10.182] [PMID: 30551398]
[31]
van Beek, J.H.; de Moor, M.H.; de Geus, E.J.; Lubke, G.H.; Vink, J.M.; Willemsen, G.; Boomsma, D.I. The genetic architecture of liver enzyme levels: GGT, ALT and AST. Behav. Genet., 2013, 43(4), 329-339.
[http://dx.doi.org/10.1007/s10519-013-9593-y] [PMID: 23580007]
[32]
Gómez-Sierra, T.; Molina-Jijón, E.; Tapia, E.; Hernández-Pando, R.; García-Niño, W.R.; Maldonado, P.D.; Reyes, J.L.; Barrera-Oviedo, D.; Torres, I.; Pedraza-Chaverri, J. S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. J. Pharm. Pharmacol., 2014, 66(9), 1271-1281.
[http://dx.doi.org/10.1111/jphp.12263] [PMID: 24779924]
[33]
Gorgel, S.N.; Akin, Y.; Koc, E.M.; Kose, O.; Ozcan, S.; Yilmaz, Y. Impact of increased AST/ALT (De Ritis) ratio in prognosis of testicular cancer. Investig. Clin. Urol., 2018, 60, 169-175.
[http://dx.doi.org/10.4111/icu.2019.60.3.169] [PMID: 31098424]
[34]
Chen, S.L.; Li, J.P.; Li, L.F.; Zeng, T.; He, X. Elevated preoperative serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio is associated with better prognosis in patients undergoing curative treatment for gastric adenocarcinoma. Int. J. Mol. Sci., 2016, 17(6), 911-922.
[http://dx.doi.org/10.3390/ijms17060911] [PMID: 27294917]
[35]
Hung, H.Y.; Chen, J.S. Chien-YuhYeh; Tang, R.; Hsieh, P.S.; Wen-SyTasi; You, Y.T.; You, J.F.; Chiang, J.M. Preoperative alkaline phosphatase elevation was associated with poor survival in colorectal cancer patients. Int. J. Colorectal Dis., 2017, 32(12), 1775-1778.
[http://dx.doi.org/10.1007/s00384-017-2907-4] [PMID: 29030683]
[36]
Sharma, A.; Arora, P. Anti-cancer activity of Cedrusdeodara in 1, 2-dimethly hydrazine induced anticancer model in rats. Asian J. Pharm. Res. Dev., 2018, 6(2), 82-86.
[http://dx.doi.org/10.22270/ajprd.v6i2.348]
[37]
Liu, H.; Zhang, N.; Cui, M.; Liu, Z.; Liu, S. Probing the interactions between Cisplatin and essential amino acids using electrospray ionization mass spectrometry. Int. J. Mass Spectrom., 2016, 409, 59-66.
[http://dx.doi.org/10.1016/j.ijms.2016.09.017]
[38]
Osama, H.; Abdullah, A.; Gamal, B.; Emad, D.; Sayed, D.; Hussein, E.; Mahfouz, E.; Tharwat, J.; Sayed, S.; Medhat, S.; Bahaa, T.; Abdelrahim, M.E.A. Effect of honey and royal jelly against CP-induced nephrotoxicity in patients with cancer. J. Am. Coll. Nutr., 2017, 36(5), 342-346.
[http://dx.doi.org/10.1080/07315724.2017.1292157] [PMID: 28548561]
[39]
Kara, A.V.; Aldemir, M.N.; Ozcicek, F.; Mammadov, R.; Yazıcı, G.N.; Sunar, M.; Gulaboglu, M. Protective effect of taxifolin on CP-induced nephrotoxicity in rats. Anal. Quant. Cytopathol. Histpathol., 2019, 41, 47-54.
[40]
Nishikawa, M.; Miyake, H.; Fujisawa, M. Identification of risk factors predicting febrile neutropenia in patients with metastatic germ cell tumors receiving cisplatin-based combination chemotherapy. Int. J. Urol., 2017, 24(6), 449-453.
[http://dx.doi.org/10.1111/iju.13352] [PMID: 28421640]
[41]
Hendrickson, O.D.; Zherdev, A.V.; Gmoshinskii, I.V.; Dzantiev, B.B. Fullerenes: In vivo studies of biodistribution, toxicity, and biological action. Nanotechnol. Russ., 2014, 9(11-12), 601-617.
[http://dx.doi.org/10.1134/S199507801406010X]
[42]
Jensen, A.W.; Wilson, S.R.; Schuster, D.I. Biological applications of fullerenes. Bioorg. Med. Chem., 1996, 4(6), 767-779.
[http://dx.doi.org/10.1016/0968-0896(96)00081-8] [PMID: 8818226]
[43]
Moussa, F. [60]Fullerene and derivatives for biomedical applications. Nanobiomaterials, 2018, 113-136.
[44]
Ramachandran, K.; Venketnarayanan, R. Anti cancer potential of the extract of Melothoriamaderaspatana on DMH induced colon cancer in albino rats. Int. J. Res. Pharm. Sci., 2019, 10(3), 1770-1777.
[http://dx.doi.org/10.26452/ijrps.v10i3.1370]
[45]
Touchefeu, Y.; Montassier, E.; Nieman, K.; Gastinne, T.; Potel, G.; Bruley des Varannes, S.; Le Vacon, F.; de La Cochetière, M.F. Systematic review: The role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis - current evidence and potential clinical applications. Aliment. Pharmacol. Ther., 2014, 40(5), 409-421.
[http://dx.doi.org/10.1111/apt.12878] [PMID: 25040088]
[46]
Cheng, L.; Lai, M.D. Aberrant crypt foci as microscopic precursors of colorectal cancer. World J. Gastroenterol., 2003, 9(12), 2642-2649.
[http://dx.doi.org/10.3748/wjg.v9.i12.2642] [PMID: 14669304]
[47]
Bulus, H.; Oguztuzun, S.; Güler Simsek, G.; Kilic, M.; Ada, A.O.; Göl, S.; Kocdogan, A.K.; Kaygın, P.; Bozer, B.; Iscan, M. Expression of CYP and GST in human normal and colon tumor tissues. Biotech. Histochem., 2019, 94(1), 1-9.
[http://dx.doi.org/10.1080/10520295.2018.1493220] [PMID: 30092668]
[48]
Ushiku, T.; Raftopoulos, S.C.; Lauwers, G.Y.; Kumarasinghe, M.P. Stomach: Neoplastic patterns and mimics. In: Kumarasinghe M.; Brown, I.; Eds. Endoscopic Biopsy Interpretation; Springer: Cham, 2019; pp. 157-187.
[49]
El-Khadragy, M.F.; Nabil, H.M.; Hassan, B.N.; Tohamy, A.A.; Waaer, H.F.; Yehia, H.M.; Alharbi, A.M.; Moneim, A.E.A. Bone marrow cell therapy on 1, 2-dimethylhydrazine (DMH)-induced colon cancer in rats. Cell. Physiol. Biochem., 2018, 45(3), 1072-1083.
[http://dx.doi.org/10.1159/000487349] [PMID: 29439258]
[50]
Singh, K.; Bhori, M.; Kasu, Y.A.; Bhat, G.; Marar, T. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity - Exploring the armoury of obscurity. Saudi Pharm. J., 2018, 26(2), 177-190.
[http://dx.doi.org/10.1016/j.jsps.2017.12.013] [PMID: 30166914]
[51]
Mehdizadeh, M.; Rouhani, H.; Sepehri, N.; Varshochian, R.; Ghahremani, M.H.; Amini, M.; Gharghabi, M.; Ostad, S.N.; Atyabi, F.; Baharian, A.; Dinarvand, R. Biotin decorated PLGA nanoparticles containing SN-38 designed for cancer therapy. Artif. Cells Nanomed. Biotechnol., 2017, 45(3), 495-504.
[http://dx.doi.org/10.1080/21691401.2016.1178130] [PMID: 27137460]
[52]
Kontek, R.; Drozda, R.; Sliwinski, M.; Grzegorczyk, K. Genotoxicity of irinotecan and its modulation by vitamins A, C and E inhuman lymphocytes from healthy individuals and cancer patients. Toxicol. In Vitro, 2010, 24, 417-424.
[http://dx.doi.org/10.1016/j.tiv.2009.10.013] [PMID: 19853651]

Rights & Permissions Print Cite
Article Metrics
38
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy