Controlling the Association of Adamantyl-Substituted Poly{N- [tris(hydroxymethyl)methyl]acrylamide} and a b-Cyclodextrin/ Epichlorohydrin Polymer by a Small Drug Molecule – Naproxen by DanicaMislovic ˇova ´ a ), GrigorijKogan a ), Noe ¨lleMartineGosselet b ), BernardSe ´bille b ),and Ladislav S ˇ olte ´s* c ) a )Institute of Chemistry, Slovak Academy of Sciences, SK-84538 Bratislava b ) Laboratoire de Recherche sur les Polyme `res, UMR 7581, CNRS, F-94320 Thiais c )Institute of Experimental Pharmacology, Slovak Academy of Sciences, SK-84104 Bratislava (fax/phone: þ 421-2-5477-5928; e-mail: ladislav.soltes@savba.sk) Two polymeric substances, a poly{N-[tris(hydroxymethyl)methyl]acrylamide} (THMMA) substi- tuted with adamantyl moieties and a b-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 b- cyclodextrin cavities, thus expulsing adamantyl moieties, led to disruption of such association and inhibitionofgelformation.Theconditionsrequiredfortheassociationofthetwopolymericcomponents andformationofthegel,aswellasthedynamicsofitsinhibitionbyadditionofnaproxenwasestablished. Theprocedureofusingsolutionsoftwoassociatingpolymersandanappropriatedrugcompetitorcanbe used at targeted viscosupplementation. 1.Introduction. –Theadamantanemoleculefitssnuglyintotheinternalcavityof b- cyclodextrin forming a host–guest associate (cf . Fig.1).Thestabilityconstant(log K) ofacomplexbetween, e.g.,water-soluble b-cyclodextrinandhydrophobicadamantane- 1-carboxylate in H 2 O at pH7.0 or 7.2 equals 4.60  0.02 or 4.51  0.02 [1]. Thus, cyclodextrin (CD) is often used as a mediator at (dissolution) of small hydrophobic molecules in aqueous media [2]. CHEMISTRY & BIODIVERSITY – Vol.4 (2007) 52 # 2007 Verlag Helvetica Chimica Acta AG, Zürich Fig.1. Host–Guest Associate of b-Cyclodextrin (blue) and Adamantane (red) Molecules