Citric acid-γ-cyclodextrin crosslinked oligomers as carriers for doxorubicin delivery

被引：0
作者：
Resmi Anand
Milo Malanga
Ilse Manet
Francesco Manoli
Kata Tuza
Ahmet Aykaç
C. Ladavière
Eva Fenyvesi
Antonio Vargas-Berenguel
Ruxandra Gref
Sandra Monti
机构：
[1] Institute for Organic Synthesis and Photoreactivity,CycloLab
[2] CNR,Departamento de Química y Física
[3] Cyclodextrin R&D Ltd.,undefined
[4] Universidad de Almería,undefined
[5] Ecole Polytechnique Universitaire Lyon,undefined
[6] UMR 8612 CNRS Université Paris-Sud,undefined
来源：
Photochemical & Photobiological Sciences | 2013年 / 12卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Two citric acid crosslinked γ-cyclodextrin oligomers (pγ-CyD) with a MW of 21-33 kDa and 10-15 γ-CyD units per molecule were prepared by following green chemistry methods and were fully characterized. The non-covalent association of doxorubicin (DOX) with these macromolecules was investigated in neutral aqueous medium by means of circular dichroism (CD), UV-vis absorption and fluorescence. Global analysis of multiwavelength spectroscopic CD and fluorescence titration data, taking into account the DOX monomer-dimer equilibrium, evidenced the formation of 1?:?1 and 1?:?2 pγ-CyD unit-DOX complexes. The binding constants are 1-2 orders of magnitude higher than those obtained for γ-CyD and depend on the characteristics of the oligomer batch used. The concentration profiles of the species in solution evidence the progressive monomerization of DOX with increasing oligomer concentration. Confocal fluorescence imaging and spectral imaging showed a similar drug distribution within the MCF-7 cell line incubated with either DOX complexed to pγ-CyD or free DOX. In both cases DOX is taken up into the cell nucleus without any degradation.
引用
收藏
页码：1841 / 1854
页数：13
相关论文
共 313 条
  • [1] Dal Ben D(2007)DNA topoisomerase II structures and anthracycline activity: insights into ternary complex formation Curr. Pharm. Des. 13 2766-2780
  • [2] Palumbo M(2004)Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity Pharmacol. Rev. 56 185-229
  • [3] Zagotto G(2003)Pharmacokinetics of pegylated liposomal doxorubicin - Review of animal and human studies Clin. Pharmacokinet. 42 419-436
  • [4] Capranico G(2001)Pegylated liposomal doxorubicin: Metamorphosis of an old drug into a new form of chemotherapy Cancer Invest. 19 424-436
  • [5] Moro S(2004)Cyclodextrin-based pharmaceutics: Past, present and future Nat. Rev. Drug Discovery 3 1023-1035
  • [6] Minotti G(2013)Nanostructures of Cationic Amphiphilic Cyclodextrin Complexes with DNA Biomacromolecules 14 811-817
  • [7] Menna P(2009)Cyclodextrin-Based Polymeric Materials: Synthesis, Properties, and Pharmaceutical/Biomedical Applications Biomacromolecules 10 3157-3175
  • [8] Salvatorelli E(1997)Methyl-beta-cyclodextrin in HL-60 parental and multidrug-resistant cancer cell lines: effect on the cytotoxic activity and intracellular accumulation of doxorubicin Cancer Chemother. Pharmacol. 40 489-494
  • [9] Cairo G(1998)Antiproliferative effect of methyl-beta-cyclodextrin Br. J. Cancer 78 1165-1169
  • [10] Gianni L(1998) and in human tumour xenografted athymic nude mice Eur. J. Cancer 34 168-174
12345678910