title: Citric acid-γ-cyclodextrin crosslinked oligomers as carriers for doxorubicin delivery.
abstract: 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.
authors.affiliation: Institute for Organic Synthesis and Photoreactivity, CNR, via P. Gobetti 101, 40129 Bologna, Italy. sandra.monti@isof.cnr.it.
authors.forename: Resmi
authors.initials: R
authors.lastname: Anand
authors.forename: Milo
authors.initials: M
authors.lastname: Malanga
authors.forename: Ilse
authors.initials: I
authors.lastname: Manet
authors.forename: Francesco
authors.initials: F
authors.lastname: Manoli
authors.forename: Kata
authors.initials: K
authors.lastname: Tuza
authors.forename: Ahmet
authors.initials: A
authors.lastname: Aykaç
authors.forename: C
authors.initials: C
authors.lastname: Ladavière
authors.forename: Eva
authors.initials: E
authors.lastname: Fenyvesi
authors.forename: Antonio
authors.initials: A
authors.lastname: Vargas-Berenguel
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.forename: Sandra
authors.initials: S
authors.lastname: Monti
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002942:Circular Dichroism; D019343:Citric Acid / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D011108:Polymers / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D011108:Polymers; D047408:gamma-Cyclodextrins; D019343:Citric Acid; D004317:Doxorubicin; C023792:gamma-cyclodextrin