Engineered beta-cyclodextrin-based carrier for targeted doxorubicin delivery in breast cancer therapy in vivo

Hoon Hyun; Sungsu Lee; Wonbong Lim; Danbi Jo; Jin Seok Jung; Gayoung Jo; So Yeon Kim; Deok-Won Lee; Sewook Um; Dae Hyeok Yang; Heung Jae Chun

Journal of Industrial and Engineering Chemistry, Vol.70, 145-151, February, 2019

DOI10.1016/j.jiec.2018.09.052 Export Citation

Engineered beta-cyclodextrin-based carrier for targeted doxorubicin delivery in breast cancer therapy in vivo

Hoon Hyun, Sungsu Lee¹, Wonbong Lim², Danbi Jo, Jin Seok Jung, Gayoung Jo, So Yeon Kim³, Deok-Won Lee⁴, Sewook Um⁵, Dae Hyeok Yang^{6, †}, and Heung Jae Chun⁷

Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea
¹Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School, Gwangju 61469, Republic of Korea
²Department of Premedical Program, School of Medicine, Chosun University, Gwangju 61452, Republic of Korea
³Department of Dental Hygiene, College of Health Sciences, Cheongju University, Cheongju 28503, Republic of Korea
⁴Department of Oral & Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gangdong, Kyung Hee University, Seoul 153-782, Republic of Korea
⁵Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea
⁶Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
⁷Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea

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In this study, we prepared a beta-cyclodextrin (β-CD)-based carrier consisting of β-CD, polyethylene glycol (PEG) and folic acid (FA) (CDPF) for improved doxorubicin (DOX) delivery to targeted breast cancer in vitro and in vivo. The morphology and size distribution were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements, which revealed in particles ranging from 38 nm to 52 nm in size. DOX from CDPF was released in a sustained manner for 48 h. Cell viability analysis showed the low toxicity of free DOX, whereas CDPF-DOX remarkably exhibited reduced viability after incubation for 7 days. In vivo animal test showed that intravenous injection of CDPF-DOX contributes to decreased tumor volume, along with no systemic toxicity and cardiotoxicity. The results suggested that CDPF can maximize the efficacy of DOX delivery; therefore can be used as a good candidate for developing optimal drug delivery systems.

Keywords:Beta-cyclodextrin (β-CD);Polyethylene glycol (PEG);Folic acid (FA);Doxorubicin (DOX);Breast cancer therapy

[References]

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[Referenced By]

[1] Meier R, Henning TD, Boddington S, Tavri S, Arora S, Piontek G, Rudelius M, Corot C, Daldrup-Link HE, Radiology, 255, 527 (2010)

[2] Lindley C, McCune JS, Thomason TE, Lauder D, Sauls A, Adkins S, Sawyer WT, Cancer Pract., 7, 59 (1999)

[3] Zhao CY, Cheng R, Yang Z, Tian ZM, Molecules, 23, 826 (2018)

[4] Avgoustakis K, Beletsi A, Panagi Z, Klepetsanis P, Karydas AG, Ithakissios DS, J. Control. Release, 79, 123 (2002)

[5] Lee DW, Jo JH, Jo DB, Kim JH, Min JJ, Yang DH, Hyun H, J. Ind. Eng. Chem., 57, 37 (2018)

[6] Wang W, Zhang Y, Yang Q, Sun M, Fei X, Song Y, Zhang Y, Yaoxian L, Nanoscale, 5, 4958 (2013)

[7] Heo DN, Yang DH, Moon HJ, Lee JB, Bae MS, Lee SC, Lee WJ, Sun IC, Kwon IK, Biomaterials, 33, 856 (2012)

[8] Santos EC, da S, Wantanabe A, Vargas MD, Tanaka MN, Garcia F, Ronconi CM, New J. Chem., 42, 671 (2018)

[9] Muller C, Schubiger PA, Schibli R, Eur. J. Nucl. Med. Mol. Imaging, 33, 1162 (2006)

[10] Bao Y, Guegain E, Mougin J, Nicolas J, Polym. Chem., 9, 687 (2018)

[11] Yousef T, Hassan N, J. Macromol. Chem., 87, 105 (2017)

[12] Hyun H, Park MH, Lim W, Kim SY, Jo DB, Jung JS, Um S, Lee DW, Yang DH, Artif Cells Nanomed Biotechnol., 11, 1 (2018)

[13] Liu L, Guo QX, J. Incl. Phemnom. Macro. Chem., 42, 1 (2002)

[14] Loftsson T, Brewster ME, J. Pharm. Sci., 10, 1017 (1996)

[15] Ryzhakov A, Do Thi T, Stappaerts J, Bertoletti L, Kimpe K, Sa Couto AR, et al., J. Pharm. Sci., 105, 2556 (2016)

[16] Messner M, Kurkov SV, Flavia-Piera R, Brewster ME, Loftsson T, Int. J. Pharm., 408, 235 (2011)

[17] Fulop Z, Gref R, Luftsson T, Int. J. Pharm., 454, 559 (2013)

[18] Ren W, Iqbal MZ, Zeng L, Chen T, Pan Y, Zhao J, Yin H, Zhang L, Zhang J, Li A, Wu A, Nanoscale, 9, 11195 (2017)

[19] Gidwani B, Vyas A, Biomed. Res. Int.15 ArticleID 198268 (2015).

[20] Li JM, Zhang W, Su H, Wang YY, Tan CP, Ji LN, Mao ZW, Int. J. Nanomed., 10, 3147 (2015)

[21] Gao W, Chan JM, Farokhzad OC, Mol. Pharm., 7, 1913 (2010)

[22] Onodera R, Motoyama K, Okamatsu A, Higashi T, Arima HR, Sci. Rep., 3, 1104 (2013)

[23] Grosse PY, Bressolle F, Pinguet F, Br. J. Cancer, 78, 1164 (1998)

[24] Qiu N, Li X, Liu J, J. Incl. Phenom. Macro. Chem., 89, 229 (2017)

[25] Suzuki F, Hashimoto K, Kikuchi H, Nishikawa H, Matsumoto H, Shimada J, Kawase K, Sunaga K, Tsuda T, Satoh K, Sakagami H, Anticancer Res., 25, 887 (2005)

[26] Green DR, Cell, 102, 1 (2000)

[27] Bushman J, Vaughan A, Sheihet L, Zhang Z, Costache M, Kohn J, J. Control. Release, 171, 315 (2013)

[28] Bazak R, Houri M, Achy SE, Hussein W, Refaat T, Mol. Clin. Oncol., 2, 904 (2014)

[29] Bazak R, Houri M, El Achy S, Kamel S, Refaat T, J. Cancer Res. Clin. Oncol., 141, 769 (2015)

[30] Gullotti E, Yeo Y, Mol. Pharm., 6, 1041 (2009)

[31] Kreute J, Int. J. Pharm., 331, 1 (2007)

[32] Gustafson HH, Holt-Casper D, Grainger DW, Ghandehari H, Nano Today, 10(4), 487 (2015)

[33] Suk JS, Xu NQ, Kim N, Hanes J, Ensign LM, Adv. Drug Deliv. Rev., 99, 28 (2016)

[34] Gottesman MM, Fojo T, Bates SE, Nat. Rev. Cancer, 2, 48 (2002)

[35] Peer D, Karp JM, Hong S, FaroKHzad OC, Margalit R, Langer R, Nat. Nanotechnol., 2(12), 751 (2007)

[36] De Lange JH, Schipper NW, Schuurhuis GJ, ten Kate TK, van Heijningen HM, Pinedo HM, Lankelma J, Baak JPA, Cytometry., 13, 571 (1992)

[37] Chatterjee K, Zhang J, Honbo N, Karliner JS, Cardiology, 115, 115 (2010)