ABSTRACT
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
New associative pH sensitive systems composed of a modified dextran bearing 2-carboxycyclohexyl carboxyl groups and neutral (p betaCD) or positively charged (p betaCDN(+))beta-cyclodextrin-co-epichlorhydrin copolymers have been synthesized and their properties were investigated as a function of pH by phase diagrams and viscosimetry. The affinity between the CD cavities and the hydrophobic guests (2-carboxycyclohexyl carboxyl groups) has been studied as a function of pH. The system with the neutral p betaCD shows a pH dependent behavior due to the lowest affinity of the guest at pH above 5 for the cavity. Associative phase separation is produced at low pH whereas soluble complexes occur at higher pH. The opposite trend is observed with the system containing the cationic p betaCDN(+). This behavior is due to the combination of electrostatic and inclusion complex interactions in this system. Addition of salt, by screening the electrostatic interactions, also strongly influences the response of the system.
