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Drug Release Profile and Cellular Uptake of Polymeric Prodrugs Synthesized from Amphiphilic Blockcopolymer Using Mechanically Produced Macromonomers Possessing Anhydrate as a Terminal Group

Authors

  • Shin-ichi Kondo

    Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan

  • Sayaka Kimura

    Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan

  • Kenjiro Tatematsu

    Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan

  • Yuka Sawama

    Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan

  • Naoki Doi

    Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan

  • Yasushi Sasai

    Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan

  • Yukinori Yamauchi

    Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

  • Masayuki Kuzuya

    Chubu Gakuin University, 2-1 Kirigaoka, Seki-shi, Gifu 501-3993, Japan

DOI:

https://doi.org/10.6000/1927-5951.2016.06.01.5

Keywords:

Polymeric micelle, macromonomer, maleic anhydride, drug release.

Abstract

In this paper, the polymeric micelle was fabricated with amphiphilic block copolymer which was synthesized by the condensation of mechanochemically produced PBzMA macromonomer with a-methyl-w-aminopropoxy polyoxyethylene. Although the polymeric micelles containing 5-fluorouracil (5-FU) or rohdamine showed the narrow size distribution as well as blank polymeric micelles, the particle diameter of the polymeric micelles containing 5-FU or rohdamine was larger than that of blank polymeric micelle. Polymeric micelle containing 5-FU slowly released 5-FU and about 10 % of 5-FU was released within 72 h. The present polymeric micelle was uptaken by A549 cells, but HepG2 cells did not. Cytotoxicity of Polymeric micelle containing 5-FU was not observed against HepG2 and A549 cells in this experimental condition. It was considered that the slow release of 5-FU from Polymeric micelle might cause the insufficient cytotoxicity.

References

Yokoyama M, Miyauchi M, Yamada N, Okano T, Kataoka K, Inoue S. Polymer micelles as novel drug carrier: adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. J Control Rel 1990; 11: 269-278. http://dx.doi.org/10.1016/0168-3659(90)90139-K

Kohori F, Sakai K, Aoyagi T, Yokoyama M, Sakurai Y, Okano T. Preparation and characterization of thermally responsive block copolymer micelles comprising poly (N-isopropylacrylamide-b-DL-lactide). J Control Rel 1998; 55: 87-98. http://dx.doi.org/10.1016/S0168-3659(98)00023-6

Yasugi K, Nagasaki Y, Kato M, Kataoka K. Preparation and characterization of polymer micelles from poly(ethylene glycol)-poly(D,L-lactide) block copolymers as potential drug carrier. J Control Rel 1999; 62: 89-100. http://dx.doi.org/10.1016/S0168-3659(99)00028-0

Akiyoshi K, Kang E-C, Kurumada S, Sunamoto J, Principi T, Winnik FM. Controlled association of amphiphilic polymers in water: thermosensitive nanoparticles formed by self-assembly of hydrophobically modified pullulans and poly(N-isopropylacrylamides). Macromolecules 2000; 33: 3244-3249. http://dx.doi.org/10.1021/ma991798d

Katayama Y, Sonoda T, Maeda M. A polymer micelle responding to the protein kinase a signal. Macromolecules 2001; 34: 8569-8573. http://dx.doi.org/10.1021/ma010966a

Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev 2001; 47: 113-131 and references cited therein.

Savic R, Luo L, Eisenberg A, Maysinger D. Micellar nanocontainers distribute to defined cytoplasmic organelles. Science 2003; 300: 615-618. http://dx.doi.org/10.1126/science.1078192

Francis MF, Cristea M, Winnik FM. Polymeric micelles for oral drug delivery : Why and how. Pure Appl Chem 2004; 76: 1321-1335, and references cited therein.

Djordjevic J, Barch M, Uhrich KE. Polymeric micelles based on amphiphilic scorpion-like macromolecules: novel carriers for water-insoluble drugs. Pharm Res 2005; 22: 24-32. http://dx.doi.org/10.1007/s11095-004-9005-3

Bae Y, Nishiyama N, Fukushima S, Koyama H, Yasuhiro M, Kataoka K. Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjugate Chem 2005; 16: 122-130. http://dx.doi.org/10.1021/bc0498166

Ito K. Polymeric design by macromonomer technique. Prog Polym Sci 1998; 23: 581-620. http://dx.doi.org/10.1016/S0079-6700(97)00049-X

Ito K, Kawaguchi S. Poly(macromonomers): homo-and copolymerization . Adv Polym Sci 1999; 142: 129-178. http://dx.doi.org/10.1007/3-540-68310-0_3

Maniruzzaman M, Kawaguchi S, Ito K. Micellar copolymerization of styrene with poly(ethylene oxide) macromonomer in water: approach to unimolecular nanoparticles via pseudo-liming radical polymerization. Macromolecules 2000; 33: 1583-1592. http://dx.doi.org/10.1021/ma991272t

Kondo S, Tsukamoto M, Sasai Y, Yamauchi Y, Kuzuya M. Novel synthesis of macromonomers by mechanochemical reaction for the application to polymeric micelles. J Phar Nutrit Sci 2011; 1: 124-129. http://dx.doi.org/10.6000/1927-5951.2011.01.02.06

Kondo S, Omoto M, Sawama Y, Sasai Y, Tatematsu K, Yamauchi Y, Kuzuya M. Synthesis of amphiphilic blockcopolymer using mechanically produced macromonomers possessing anhydrate as a terminal group and its application to polymeric micelles. J Phar Nutrit Sci 2014; 4: 37-42. http://dx.doi.org/10.6000/1927-5951.2014.04.01.6

Iijima M, Nagasaki Y, Okada T, Kato M, Kataoka K. Core-Polymerized Reactive Micelles from Heterotelechelic Amphiphilic Block Copolymers. Macromolecules 1999; 32: 1140-1146. http://dx.doi.org/10.1021/ma9815962

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Published

2016-01-05

Issue

Vol. 6 No. 1 (2016)

Section

Articles

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Copyright (c) 2016 Shin-ichi Kondo, Sayaka Kimura, Kenjiro Tatematsu, Yuka Sawama, Naoki Doi, Yasushi Sasai, Yukinori Yamauchi, Masayuki Kuzuya

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

How to Cite

Drug Release Profile and Cellular Uptake of Polymeric Prodrugs Synthesized from Amphiphilic Blockcopolymer Using Mechanically Produced Macromonomers Possessing Anhydrate as a Terminal Group . (2016). Journal of Pharmacy and Nutrition Sciences , 6(1), 27-32. https://doi.org/10.6000/1927-5951.2016.06.01.5

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