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.

Aminocyclodextrin Oligomers as Protective Agents of Protein Aggregation

“…Giglio CyD oligomers andp olymers can exhibit ad ramatic enhancement of the inclusion ability towards various guest molecules. [30][31][32][33] For this reason, in the last years they have gained great attention from the pharmaceutical industry. [34] Successful examples of linear CyD polymers specifically designed as drug carriers are Cyclosert [35] and CALAA-01.…”

Cyclodextrin‐Based Macromolecular Systems as Cholesterol‐Mopping Therapeutic Agents in Niemann–Pick Disease Type C

“…CCPs have been employed in designing assemblies (hydrogels, micelles, and nanoparticles) with a range of bio‐applications, from complexing disinfecting drugs for control release in wound and burn treatments to delivery vehicles for nucleic acids, from the construction of biosensors for cocaine to sophisticated host–guest assemblies for regenerative medicine . In general, CCPs offer several advantages over the simple monomeric CDs, such as: i) improved water solubility for the presence of several CD units, ii) higher catalytic effect and iii) greater drug‐loading capacity . The improved binding abilities are essentially due to the cooperation of several adjacent CD moieties to bind guest molecules that are too large to be accommodated in a single CD cavity .…”

Controllable drug uptake and nongenomic response through estrogen-anchored cyclodextrin drug complex

“…29 The effect of varying CDE 1 concentrations on the fluorescence intensity of Ada-DOX was examined in order to determine the association constant (K d ) between CDE 1 and Ada-DOX. The concentration of Ada-DOX was set at 50 µM in the presence of CDE 1 at escalating concentrations of 0, 0.17, 0.26, 0.35, 0.44, 0.53, 0.62, 0.71, 0.79, and 0.88 mM, and the fluorescence intensity was monitored using a Synergy™ H4 Hybrid Microplate Reader (BioTek Inc., Winooski, VT, USA).…”

“…The host-guest binding affinity of CDE 1 with Ada-DOX (K d ) was measured using the fluorescence titration method as described previously. 29 With an increasing amount of CDE 1 added to the dimethylformamide and H 2 O (1:1) solution containing Ada-DOX, the fluorescence intensity was measured at varying emission wavelengths from 500 to 700 nm with 600 nm as the maximum peak, which decreased in a concentration-dependent manner ( Figure 2C). The K d values were calculated using the fluorescence intensity versus CDE 1 concentration curve.…”