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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Release Kinetics of 6-Mercaptopurine and 6-Thioguanine from Bioinspired Core-Crosslinked Thymine Functionalised Polymeric Micelles

Gagan Kaur A , Milton T. W. Hearn A , Toby D. M. Bell A and Kei Saito A B
+ Author Affiliations
- Author Affiliations

A School of Chemistry, Monash University, Clayton, Vic. 3800, Australia.

B Corresponding author. Email: kei.saito@monash.edu

Australian Journal of Chemistry 66(8) 952-958 https://doi.org/10.1071/CH13125
Submitted: 19 March 2013  Accepted: 30 April 2013   Published: 22 May 2013

Abstract

A bioinspired core-bound polymeric micellar system based on hydrogen bonding and photo-crosslinking of thymine has been prepared from the amphiphilic block copolymers, poly(vinylbenzylthymine)-block-poly(vinylbenzyltriethylammonium chloride). The chemical loading and controlled release potential of these micelles was investigated using two drugs, 6-mercaptopurine and 6-thioguanine. The release kinetics of drug-loaded polymeric micelles was determined by pressure ultrafiltration and the effects of hydrogen bonding, core-crosslinking, and core size on the loading capacity and release kinetics were analysed. The results demonstrate that drug release rates are affected by hydrogen bonding in the micelle core. Furthermore, these studies indicate that drug release rates can be controlled by changing the size of the core and by photo-crosslinking thymine groups in the core.


References

[1]  N. Nishiyama, Y. Bae, K. Miyata, S. Fukushima, K. Kataoka, Drug Discov. Today: Technol. 2005, 2, 21.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXpvFOmt7w%3D&md5=78f460ac018b9dcedbf1265f25ca9b72CAS |

[2]  N. Nishiyama, K. Kataoka, Pharmacol. Therapeut. 2006, 112, 630.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFSksr7P&md5=59ebad171d783b21a7f65dc8ce52e49dCAS |

[3]  V. P. Torchilin, Pharm. Res. 2007, 24, 1.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1yis7rM&md5=711fa78d17d31767c47eaca116e11e26CAS | 17109211PubMed |

[4]  Y. Matsumura, K. Kataoka, Cancer Sci. 2009, 100, 572.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlsFSrs7g%3D&md5=6220a5a3ae7b33b59dbbca0e32a4c70dCAS | 19462526PubMed |

[5]  J. Gong, M. Chen, Y. Zheng, S. Wang, Y. Wang, J. Controlled Release 2012, 159, 312.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XisFKgtbc%3D&md5=ecb1f8aa4af50d21c0d019613435d973CAS |

[6]  Y. Tian, S. Mao, Expert Opin. Drug Deliv. 2012, 9, 687.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XnsFCqtLo%3D&md5=4819cd57cf284beac7325566f034487eCAS | 22519507PubMed |

[7]  X.-B. Xiong, Z. Binkhathlan, O. Molavi, A. Lavasanifar, Acta Biomater. 2012, 8, 2017.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XmsVGqsrY%3D&md5=07a67b63efbdb54d46e6cfcdd144ad37CAS | 22406912PubMed |

[8]  V. P. Torchilin, J. Controlled Release 2001, 73, 137.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXksVSqtbo%3D&md5=4c0e486e56a0e801f01ab5bf6828a55bCAS |

[9]  S. C. Owen, D. P. Y. Chan, M. S. Shoichet, Nano Today 2012, 7, 53.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xjt1Omtbk%3D&md5=fed1e2dbc81ffa1376b4aa77e469a112CAS |

[10]  K. Kataoka, A. Harada, Y. Nagasaki, Adv. Drug Deliv. Rev. 2001, 47, 113.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhvVajs78%3D&md5=b774c3eda22537c30c1cb685a7f8d043CAS | 11251249PubMed |

[11]  K. Kataoka, A. Harada, Y. Nagasaki, Adv. Drug Deliv. Rev. 2012, 64, 37.
         | Crossref | GoogleScholarGoogle Scholar |

[12]  J. M. Rabanel, V. Aoun, I. Elkin, M. Mokhtar, P. Hildgen, Curr. Med. Chem. 2012, 19, 3070.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVOhtr7N&md5=d03675f875cbf72bbd5b4be3a98f6b75CAS | 22612696PubMed |

[13]  R. K. O’Reilly, C. J. Hawker, K. L. Wooley, Chem. Soc. Rev. 2006, 35, 1068.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFSgtL7L&md5=91ee07a860657dd89b53201de2d7b0c1CAS | 17057836PubMed |

[14]  X.-B. Xiong, A. Falamarzian, S. M. Garg, A. Lavasanifar, J. Controlled Release 2011, 155, 248.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlWmt7jO&md5=05a82d6de398a340b097043e456f97beCAS |

[15]  C. F. van Nostrum, Soft Matter 2011, 7, 3246.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjsFymu7g%3D&md5=9387aa13af9f41eb7b9614e24c9094d7CAS |

[16]  L. Zhang, T. L. U. Nguyen, J. Bernard, T. P. Davis, C. Barner-Kowollik, M. H. Stenzel, Biomacromolecules 2007, 8, 2890.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXovFOntLs%3D&md5=fc303d6e303444357cfbad4047ba426bCAS | 17691844PubMed |

[17]  W. Lin, D. Kim, Langmuir 2011, 27, 12090.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFSmtrbL&md5=e5a00d46eb5f4a58761316e3b8eece45CAS | 21861467PubMed |

[18]  Q. Jin, S. Maji, S. Agarwal, Polym. Chem. 2012, 3, 2785.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1yksrfM&md5=ea329ee3626d38ff8a0aef741c001ba4CAS |

[19]  C. J. Rijcken, C. J. Snel, R. M. Schiffelers, C. F. van Nostrum, W. E. Hennink, Biomaterials 2007, 28, 5581.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1WqtbfI&md5=c77fc9ff15ccc6fbd29a2954f4a16e8aCAS | 17915312PubMed |

[20]  M. Danquah, T. Fujiwara, R. I. Mahato, J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 347.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsFantbzP&md5=19b11724114758b34aded5052c436742CAS |

[21]  S. M. Garg, X.-B. Xiong, C. Lu, A. Lavasanifar, Macromolecules 2011, 44, 2058.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXivFCitbo%3D&md5=2a052cd48dd21e62e045e526f7699262CAS |

[22]  Z. Zhang, L. Yin, C. Tu, Z. Song, Y. Zhang, Y. Xu, R. Tong, Q. Zhou, J. Ren, J. Cheng, ACS Macro Lett. 2013, 2, 40.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVyksbzN&md5=544de85d047f4c20ed6ed3d679ec76e9CAS | 23536920PubMed |

[23]  J. O. Kim, G. Sahay, A. V. Kabanov, T. K. Bronich, Biomacromolecules 2010, 11, 919.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjs1Crsb8%3D&md5=6dff8dc1907772ff907371d1274827a0CAS | 20307096PubMed |

[24]  M.-C. Jones, J.-C. Leroux, Eur. J. Pharm. Biopharm. 1999, 48, 101.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmtVymurk%3D&md5=6fc47c7b21ab7935e1f5393525fe2e35CAS |

[25]  U. Kedar, P. Phutane, S. Shidhaye, V. Kadam, Nanomedicine 2010, 6, 714.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlSmsLg%3D&md5=e84325547afc4d6e80a88bd24fb0c997CAS | 20542144PubMed |

[26]  S. Parveen, R. Misra, S. K. Sahoo, Nanomedicine 2012, 8, 147.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xos12htQ%3D%3D&md5=c1d4d1506e61313735a7375cffa0cd74CAS | 21703993PubMed |

[27]  N. Rapoport, Prog. Polym. Sci. 2007, 32, 962.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXovFeksb4%3D&md5=22197e143bce74b99905293cca88f663CAS |

[28]  L. Zhu, V. P. Torchilin, Integr. Biol. 2013, 5, 96.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVOrsbzK&md5=bc75d553ad38c70809811c8598a8d100CAS |

[29]  M. Talelli, W. E. Hennink, Nanomedicine 2011, 6, 1245.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1SqtbbM&md5=b2ed94a9bde1dfdca77988d1fa5bdd0cCAS | 21929459PubMed |

[30]  H. Wei, X.-Z. Zhang, Y. Zhou, S.-X. Cheng, R.-X. Zhuo, Biomaterials 2006, 27, 2028.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht12isLfL&md5=1e06bb74b10a5b2f408e0d27511a1441CAS | 16225918PubMed |

[31]  E. S. Lee, K. Na, Y. H. Bae, J. Controlled Release 2003, 91, 103.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXmsVSkur4%3D&md5=137ab4d5137fb182dbac61ad6424b3bdCAS |

[32]  N. Rapoport, Int. J. Hyperthermia 2012, 28, 374.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xns1Sks7o%3D&md5=9de70edb5bc404d638a132985711862eCAS | 22621738PubMed |

[33]  J. Jiang, X. Tong, Y. Zhao, J. Am. Chem. Soc. 2005, 127, 8290.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktFOltLk%3D&md5=314bba7444a15106e887b7d337ffca0fCAS | 15941255PubMed |

[34]  J. Šponer, J. Leszczynski, P. Hobza, Biopolymers 2001, 61, 3.
         | Crossref | GoogleScholarGoogle Scholar | 11891626PubMed |

[35]  A. A. Henry, F. E. Romesberg, Curr. Opin. Chem. Biol. 2003, 7, 727.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptlyksbg%3D&md5=53f955db58e77a3cf26c70e37f5886cfCAS | 14644182PubMed |

[36]  R. Beukers, A. P. M. Eker, P. H. M. Lohman, DNA Repair (Amst.) 2008, 7, 530.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXitVOkt7w%3D&md5=3fc1eb2f31b2f9ea4cd3ee2f01ccbe68CAS |

[37]  Y. Inaki, H. Hiratsuka, J. Photopolym. Sci. Technol. 2000, 13, 739.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhtVShu7c%3D&md5=7ff535a1cdd65bac66051ee6dabbe28aCAS |

[38]  P. Johnston, C. Braybrook, K. Saito, Chem. Sci. 2012, 3, 2301.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XotFGku7Y%3D&md5=aefdfc45941ad35626f464b0c4320204CAS |

[39]  G. Kaur, S. L. Y. Chang, T. D. M. Bell, M. T. W. Hearn, K. Saito, J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 4121.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXos1yqt70%3D&md5=f4ce968e8fd81b62aaaeb0f0d392db97CAS |

[40]  M. C. Dubinsky, Clin. Gastroenterol. Hepatol. 2004, 2, 731.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXotFWrsrY%3D&md5=42ea8b6ed57a3224d70e6b9850175cc8CAS | 15354273PubMed |

[41]  S. Coulthard, L. Hogarth, Invest. New Drugs 2005, 23, 523.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XmsFOktQ%3D%3D&md5=963429c242a20e5cb690bed9e2712fa9CAS | 16267626PubMed |

[42]  A. F. Y. Al Hadithy, N. K. H. de Boer, L. J. J. Derijks, J. C. Escher, C. J. J. Mulder, J. R. B. J. Brouwers, Dig. Liver Dis. 2005, 37, 282.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktFantLk%3D&md5=c07f32b6bcc2f5a451de5954b6b6b936CAS |

[43]  P. Karran, Br. Med. Bull. 2006, 79–80, 153.
         | Crossref | GoogleScholarGoogle Scholar | 17277075PubMed |

[44]  G. B. Elion, E. Burgi, G. H. Hitchings, J. Am. Chem. Soc. 1952, 74, 411.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG3sXltFegtA%3D%3D&md5=411aa2240484b56b61be935716387e2bCAS |

[45]  J. Šponer, J. Leszczynski, P. Hobza, J. Phys. Chem. A 1997, 101, 9489.
         | Crossref | GoogleScholarGoogle Scholar |

[46]  J. Bohon, C. R. de los Santos, Nucleic Acids Res. 2003, 31, 1331.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXit1ylsbY%3D&md5=274cf88974bdfcbb5d3b7f21a604c0d3CAS | 12582253PubMed |

[47]  J. N. Latosińska, J. Seliger, V. Žagar, D. V. Burchardt, J. Phys. Chem. A 2009, 113, 8781.
         | Crossref | GoogleScholarGoogle Scholar | 19572681PubMed |

[48]  M. F. Cunningham, M. Xie, K. B. McAuley, B. Keoshkerian, M. K. Georges, Macromolecules 2002, 35, 59.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXosFCqu74%3D&md5=2db6a1d8f977a9d76dc24ea5ef6056c4CAS |

[49]  S. E. Shim, S. Oh, Y. H. Chang, M. J. Jin, S. Choe, Polymer 2004, 45, 4731.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXksl2mt7g%3D&md5=a193c1bd5bdfedc9200f551faf61a48cCAS |

[50]  K. Saito, L. R. Ingalls, J. Lee, J. C. Warner, Chem. Commun. 2007, 2503.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmtlWmu74%3D&md5=914719c0f03eb43eb9a5dce578a6a9d4CAS |

[51]  P.-F. Yue, X.-Y. Lu, Z.-Z. Zhang, H.-L. Yuan, W.-F. Zhu, Q. Zheng, M. Yang, AAPS PharmSciTech 2009, 10, 376.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXovFansbk%3D&md5=6fab8a8f8926d8271259b6123cd0c126CAS | 19381837PubMed |

[52]  Y. Zambito, E. Pedreschi, G. Di Colo, Int. J. Pharm. 2012, 434, 28.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVOisL7N&md5=9d36ebf5cc6695426ffc45f44b5678f7CAS | 22617795PubMed |

[53]  B. Magenheim, M. Y. Levy, S. Benita, Int. J. Pharm. 1993, 94, 115.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXlvVynsL4%3D&md5=acbedc4d018b27dd0da920e5e647ac3fCAS |

[54]  S. Wallace, J. Li, R. Nation, B. Boyd, Drug Deliv. Transl. Res. 2012, 2, 284.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1Omtb3M&md5=85007e651cab1e9359af8c8a32ae6e41CAS | 23110256PubMed |

[55]  C. M. Cheng, M. I. Egbe, J. M. Grasshoff, D. J. Guarrera, R. P. Pai, J. C. Warner, L. D. Taylor, J. Polym. Sci., Part A: Polym. Chem. 1995, 33, 2515.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXotFOnu70%3D&md5=7de715957727d2581db29e5b8ca9399bCAS |

[56]  B. J. Boyd, Int. J. Pharm. 2003, 260, 239.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXkvFektL8%3D&md5=3b1f232696e14a69a7a736f005fdc970CAS | 12842343PubMed |