Abstract
For cancer treatment, anti-cancer hydrophobic drugs such as paclitaxel (PTX) are usually intravenously administrated as a systemic delivery which has low targeting efficiency, rapid clearance, and non-specific side effects. Although local chemotherapy using biomaterials to overcome these limitations has attracted attention, the poor water solubility of hydrophobic drugs is still challenging for controlled delivery and bioavailability of drugs. In this study, an in situ forming hydrogel crosslinked with PTX-loaded micelle was developed for enhanced stability and controlled delivery of PTX. Tetronic-tyramine micelle (TTAm) is a phenol-conjugated Tetronic micelle (TETm) that can facilitate enzymatic crosslinking between TTAm and gelatin-hydroxyphenyl propionic acid (GH) hydrogels to produce GH hydrogels crosslinked with TTAm (TTAm/GH) for controllable physicochemical properties such as gelation time, stiffness, and swelling ratio. The TTAm/GH showed PTX release pattern for 4 weeks in a controlled manner, whereas TETm/GH and GH only had limited release profiles. Moreover, TTAm/GH showed cytocompatibility and improved drug efficacy against cancer cells compared to the control group. Such in situ forming GH hydrogel crosslinked with Tetronic micelle is expected to be a promising local hydrophobic anti-cancer drug carrier for cancer treatment.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
Change history
28 September 2022
An Erratum to this paper has been published: https://doi.org/10.1007/s13233-022-0206-6
References
F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, CA Cancer J. Clin., 68, 394 (2018).
X. Yao, L. Chen, X. Chen, C. He, H. Zheng, and X. Chen, Colloids Surf. B: Biointerfaces, 121, 36 (2014).
J. Wang, W. Xu, S. Li, H. Qiu, Z. Li, C. Wang, X. Wang, and J. Ding, J. Biomed. Nanotechnol., 14, 2102 (2018).
L. Qin, F. Zhang, X. Lu, X. Wei, J. Wang, X. Fang, D. Si, Y. Wang, C. Zhang, R. Yang, C. Liu, and W. Liang, J. Control. Release, 171, 133 (2013).
H. T. Ta, C. R. Dass, and D. E. Dunstan, J. Control. Release, 126, 205 (2008).
E. A. Lundqvist, K. Fujiwara, and M. Seoud, Int. J. Gynaecol. Obstet., 131 Suppl 2, S146 (2015).
A. Tosti, B. M. Piraccini, C. Vincenzi, and C. Misciali, Br. J. Dermatol., 152, 1056 (2005).
V. V. Padma, BioMedicine, 5, 19 (2015).
V. Sanna, N. Pala, and M. Sechi, Int. J. Nanomed., 9, 467 (2014).
F. Celikoglu, S. I. Celikoglu, and E. P. Goldberg, Cancer Ther., 6, 545 (2008).
Y. Otani, I. Yoshida, S. Ishikawa, A. Ohtaki, S. Ohki, S. Sakata, O. Totsuka, and Y. Morishita, Jpn. J. Clin. Oncol., 26, 476 (1996).
K. L. Christman, A. J. Vardanian, Q. Fang, R. E. Sievers, H. H. Fok, and R. J. Lee, J. Am. College Cardiol., 44, 654 (2004).
B. Jeong, S. W. Kim, and Y. H. Bae, Adv. Drug Deliv. Rev., 64, 154 (2012).
L. Yu and J. Ding, Chem. Soc. Rev., 37, 1473 (2008).
D. Gu, A. J. O’Connor, G. H. Q. G, and K. Ladewig, Expert Opin. Drug Deliv., 14, 879 (2017).
M. McKenzie, D. Betts, A. Suh, K. Bui, L. D. Kim, and H. Cho, Molecules, 20, 20397 (2015).
K. Peng, I. Tomatsu, A. V. Korobko, and A. Kros, Soft Matter, 6, 85 (2010).
Y. Lu, E. Zhang, J. Yang, and Z. Cao, Nano Res., 11, 4985 (2018).
Y. Lu, X. Gao, M. Cao, B. Wu, L. Su, P. Chen, J. Miao, S. Wang, R. Xia, and J. Qian, Colloids Surf. B: Biointerfaces, 189, 110830 (2020).
L. Wang, J. Zhang, M. Song, B. Tian, K. Li, Y. Liang, J. Han, and Z. Wu, Colloids Surf. B: Biointerfaces, 152, 1 (2017).
M. Talelli, M. Barz, C. J. Rijcken, F. Kiessling, W. E. Hennink, and T. Lammers, Nano Today, 10, 93 (2015).
X. Sun, G. Wang, H. Zhang, S. Hu, X. Liu, J. Tang, and Y. Shen, ACS Nano, 12, 6179 (2018).
S. C. Owen, D. P. Chan, and M. S. Shoichet, Nano Today, 7, 53 (2012).
R. Grillo, F. V. Dias, S. M. Querobino, C. Alberto-Silva, L. F. Fraceto, E. de Paula, and D. R. de Araujo, Colloids Surf. B: Biointerfaces, 174, 56 (2019).
M. Kabiri, S. H. Kamal, S. V. Pawar, P. R. Roy, M. Derakhshandeh, U. Kumar, S. G. Hatzikiriakos, S. Hossain, and V. G. Yadav, Drug Deliv. Transl. Res., 8, 484 (2018).
T. Noda, T. Okuda, R. Mizuno, T. Ozeki, and H. Okamoto, Biol. Pharm. Bull., 41, 937 (2018).
A. C. Daly, L. Riley, T. Segura, and J. A. Burdick, Nat Rev. Mater., 5, 20 (2020).
D. Sivakumaran, D. Maitland, and T. Hoare, Biomacromolecules, 12, 4112 (2011).
P. Le Thi, J. Y. Son, Y. Lee, S. B. Ryu, K. M. Park, and K. D. Park, Macromol. Res., 28, 400 (2020).
B. Y. Kim, K. M. Park, Y. K. Joung, and K. D. Park, J. BIoact. Compat. Pol., 27, 185 (2012).
M. W. Tibbitt and K. S. Anseth, Biotechnol. Bioeng., 103, 655 (2009).
D. A. Chiappetta and A. Sosnik, Eur. J. Pharm. Biopharm., 66, 303 (2007).
M. Fernandez-Tarrio, F. Yañez, K. Immesoete, C. Alvarez-Lorenzo, and A. Concheiro, AAPS Pharmscitech, 9, 471 (2008).
Y. Lee, J. W. Bae, D. H. Oh, K. M. Park, Y. W. Chun, H. J. Sung, and K. D. Park, J. Mater. Chem. B, 1, 2407 (2013).
D. H. Oh, P. L. Thi, and K. D. Park, Macromol. Res., 30, 190 (2022).
Y. Q. Yang, B. Zhao, Z. D. Li, W. J. Lin, C. Y. Zhang, X. D. Guo, J. F. Wang, and L. J. Zhang, Acta Biomater., 9, 7679 (2013).
M. Khanmohammadi, M. B. Dastjerdi, A. Ai, A. Ahmadi, A. Godarzi, A. Rahimi, and J. Ai, Biomater. Sci., 6, 1286 (2018).
F. Lee, K. H. Bae, and M. Kurisawa, Biomed. Mater., 11, 014101 (2015).
M. McKenzie, D. Betts, A. Suh, K. Bui, L. D. Kim, and H. Cho, Molecules, 20, 20397 (2015).
K. M. Park, Y. Lee, J. Y. Son, D. H. Oh, J. S. Lee, and K. D. Park, Biomacromolecules, 13, 604 (2012).
S. Yan, J. Ren, Y. Jian, W. Wang, W. Yun, and J. Yin, Biomacromolecules, 19, 4554 (2018).
C. M. Kirschner and K. S. Anseth, Acta Mater., 61, 931 (2013).
J. Li and D. J. Mooney, Nat. Rev. Mater., 1 (2016).
T. Ito, T. Takami, Y. Uchida, and Y. Murakami, Colloids Surf. B: Biointerfaces, 163, 257 (2018).
B. Amsden, Macromolecules, 31, 8382 (1998).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Acknowledgment: This study was supported by the Priority Research Centers Program (2019R1A6A1A11051471) funded by the National Research Foundation of Korea (NRF), the Korea Medical Device Development Fund grant (RS-2020-KD000033) funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety), and the Alchemist Project of the Korea Evaluation Institute of Industrial Technology (KEIT 20018560, NTIS 1415180625) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).
Rights and permissions
About this article
Cite this article
Park, J.S., Lee, S., Oh, D.H. et al. In situ Forming Hydrogel Crosslinked with Tetronic Micelle for Controlled Delivery of Hydrophobic Anticancer Drug. Macromol. Res. 30, 811–819 (2022). https://doi.org/10.1007/s13233-022-0087-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13233-022-0087-8