Self-assembled cyclodextrin (CD)-DNA nanoparticles (CDplexes) exhibiting transfection efficiencies significantly higher than PEI-based polyplexes have been prepared from homogeneous seven-fold symmetric polyaminothiourea amphiphiles constructed on a beta-cyclodextrin scaffold.
Cationic amphiphilic beta-cyclodextrins, substituted with hydrophobic n-alkylthio chains at the primary hydroxyl side and hydrophilic omega-amino-oligo(ethylene glycol) units at the secondary side, form bilayer vesicles with a diameter of 30-35 nm (when alkyl = hexadecyl) or nanoparticles with a diameter of ca. 120 nm (when alkyl = hexyl) in water.
Novel amphiphilic cyclodextrins were synthesised by grafting oligo(ethylene glycol) units onto the secondary side of heptakis(6-alkylthio-6-deoxy)-β-cyclodextrins (alkyl = ethyl, hexyl, dodecyl and hexadecyl). The oligo(ethylene glycol) substituents were introduced by reaction of heptakis(6-alkylthio-6-deoxy)-β-cyclodextrins with ethylene carbonate in the presence of potassium carbonate at elevated temperatures. The resulting oligo(ethylene glycol)-cyclodextrin conjugates were characterised by 1 H NMR and 13 C NMR, COSY and HSQC spectroscopy, and mass spectrometry. Addition of
The amphiphilic character in water of a novel class of chemically modified cyclodextrins has been investigated by means of small-angle X-ray scattering and light scattering. The introduction ofhydrophilic oligo(ethylene glycol) onto the secondary side of heptakis[6-alkylthio-6-deoxy-2-oligo(ethylene glycol)]-beta-cyclodextrins produces an enhanced water solubility of these molecules. Shape and dimensions of the generated micellar aggregates, analyzed in terms of a suitable core-shell model, remain stable in the wide concentration range explored. The highly associative behavior of these macromolecules is evidenced by the very low value of the critical micelle concentration (cmc), which is about 2 orders of magnitude smaller than the cmc usually obtained for traditional surfactant. Despite the complex geometry of this novel macromolecule, shape and dimensions of generated micellar aggregates can be properly described according to the thermodynamic approaches generally used for amphiphilic molecules and block copolymers. Results show how the modulation of hydrophobic and hydrophilic components sensitively influence the structural features of the generated aggregates thus offering the possibility to control molecular organization in a manner similar to that for traditional colloids. For all the classes of the investigated systems, the small micelles have been found in equilibrium with polydisperse large aggregates of entangled micelles. These novel nonionic colloidal systems combine inclusion and transport properties of host macrocycles, such as cyclodextrin, together with the increased stability of colloidal aggregates, and may be of interest for their potential application as innovative drug delivery systems.
The entanglement process between water-soluble 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine and the amphiphilic cyclodextrin (CD) heptakis(2-omega-amino-O-oligo(ethylene oxide)-6-hexylthio)-beta-CD and the occurrence of various species at different porphyrin:CD ratios were studied by a combination of UV/Vis absorption, fluorescence anisotropy, time-resolved fluorescence, resonance light scattering, and circular dichroism. The effect of the entanglement process on the mean vesicle diameter was investigated over a wide concentration range by quasielastic light-scattering techniques. The experimental results indicate that the presence of porphyrins in this colloidal system promotes some structural rearrangements, essentially driven by charge interaction, which are responsible for a sensitive change of vesicle dimensions. In the range of porphyrin:CD molar ratios between 1:10 and 1:50, the porphyrin is solubilized in monomeric form (tau(1)=11.5 ns) and photosensitizes the production of singlet oxygen ((1)O(2)). At the same molar ratio the ability of this amphiphilic cyclodextrin to transport porphyrins into tumor cells indicates specificity at the nuclear-compartment level. These findings may be of potential interest for the of development agents for photodynamic therapy of tumors.
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