ABSTRACT
Novel ßCD-based hydrogels have been synthesized using sodium trimetaphosphate (STMP) as non-toxic reagent. Straightforward mixing of ßCD with dextran and STMP in basic aqueous media led to hydrogels incorporating dextran chains, phosphate groups and ßCD units. The hydrogels have been characterized by swelling measurements, XPS and (31)P NMR. The swelling ratio was correlated to the content in phosphated groups, which give a polyelectrolyte character to these hydrogels. The significant rise of the swelling ratio with the ßCD content increase has been attributed to a decrease of the number of phosphate-based crosslinks, the ßCD units playing the role of dangling ends in the tridimensional network. Their loading capacity and their release properties have been investigated for methylene blue and benzophenone in order to demonstrate their potentiality for drug delivery. Through different interaction mechanisms, electrostatic and inclusion complex interactions, these compounds are loaded with different efficiencies. The release involves deswelling, diffusion mechanisms and partition equilibrium.
Subject(s)
Cross-Linking Reagents/chemistry , Dextrans/chemistry , Drug Carriers/chemistry , Hydrogels/chemistry , Polyphosphates/chemistry , beta-Cyclodextrins/chemistry , Benzophenones/administration & dosage , Dextrans/chemical synthesis , Drug Carriers/chemical synthesis , Enzyme Inhibitors/administration & dosage , Hydrogels/chemical synthesis , Methylene Blue/administration & dosage , Photosensitizing Agents/administration & dosage , beta-Cyclodextrins/chemical synthesisABSTRACT
Novel phosphorous-containing ß-cyclodextrin (ßCD) polymers (CDP) were synthesized easily under "green chemistry" conditions. A simple polycondensation between the hydroxyl groups of ßCD and non-toxic sodium trimetaphosphate (STMP) under basic conditions led to soluble, non-reticulated CDPs with molecular weights (Mw) higher than 10(4) g mol(-1), the actual value depending on the NaOH:ßCD and STMP:ßCD weight ratios. The presence of both ßCD and phosphate groups in the polymer allows for strong interactions with amphiphilic probes, such as 1-adamantyl acetic acid, or with divalent cations, such as Ca(2+), whose strengths were characterized by isothermal titration microcalorimetry. The obtained phosphated compounds also display high affinity towards hydroxyapatite (HA), leading to HA nanoparticles that could easily be recovered by CDPs, as demonstrated by transmission electron microscopy and quantitative determination of the total amount of phosphated molecules fixed on HA.
Subject(s)
Calcium/chemistry , Durapatite/chemistry , Phosphorus/chemistry , beta-Cyclodextrins/chemistry , Molecular Weight , Polyphosphates/chemistryABSTRACT
Two polymeric substances, a poly{N-[tris(hydroxymethyl)methyl]acrylamide} (THMMA) substituted with adamantyl moieties and a beta-cyclodextrin/epichlorohydrin polycondensate, formed a host-guest type complex, which resulted in the gel formation upon mixing of these two compounds at appropriate conditions. Introduction of a drug molecule, i.e., naproxen, that was able to fill the beta-cyclodextrin cavities, thus expulsing adamantyl moieties, led to disruption of such association and inhibition of gel formation. The conditions required for the association of the two polymeric components and formation of the gel, as well as the dynamics of its inhibition by addition of naproxen was established. The procedure of using solutions of two associating polymers and an appropriate drug competitor can be used at targeted viscosupplementation.
Subject(s)
Acrylamides/chemistry , Epichlorohydrin/chemistry , Naproxen/chemistry , beta-Cyclodextrins/chemistry , Models, MolecularABSTRACT
We show here, for the first time, that two neutral polymers may completely associate together in water to spontaneously form supramolecular nanoassemblies (nanogels) of spherical shape. The cohesion of these stable structures of about 200 nm is based upon a "lock and key" mechanism: inclusion complexes are formed between the hydrophobic alkyl chains grafted on a polysaccharide (dextran) and the molecular cavities contained in a poly-cyclodextrin polymer. Production yields reached 95%. It was established that all the alkyl chains were included within the cyclodextrins' cavities in these nanoassemblies. The multivalent character of the interactions between the two polymers ensures the stability of the nanoassemblies. Moreover, empty cyclodextrin units remained accessible for the inclusion of compounds of interest such as benzophenon or tamoxifen.
Subject(s)
Drug Carriers , Gels , Nanostructures , Polymers/chemistry , Antineoplastic Agents, Hormonal/chemistry , Benzophenones/chemistry , Dextrans/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Surface Tension , Tamoxifen/chemistry , Water/chemistry , beta-Cyclodextrins/chemistryABSTRACT
The complexation of warfarin (W) enantiomers by a hydrosoluble high-molecular-weight beta-cyclodextrin/epichlohydrin polymer (EP/beta-CD polymer) was studied using HPLC with a mobile phase of methanol/0.1 M Na acetate/acetic acid (pH 4) at 22 degrees C. It was found that the complexes (W/beta-CD unit) have a 1:1 stoichiometry. The stability constants of the complex involving each enantiomer and the polymer beta-CD units were determined in the mobile phase, and the highest stability of the complex (S-warfarin/beta-CD unit) was observed. From the chromatographic separations of warfarin enantiomers on different beta-CD or its derivative supports, we have deduced the role of the simultaneous presence of several glyceryl (-O-CH(2)-CHOH-CH(2)-O-) and dihydroxypropyl (-O-CH(2)-CHOH-CH(2)OH) groups on one beta-CD ring in promoting the chiral recognition of warfarin enantiomers.
