Synthesis and characterisation of novel chemical conjugates based on α,β-polyaspartylhydrazide and β-cyclodextrins

A new family of supramolecular systems based on a synthetic polyaminoacid and cyclic oligosaccharides such as beta-cyclodextrins (beta-CDs) was synthesised. The pharmaceutical potential of these systems arises from the proper combination between the complexing properties of cyclodextrins and the particular pharmacokinetic profile that can be obtained by using macromolecular conjugates with a biocompatible backbone. Five supramolecular conjugates were synthesised by using alpha,beta-polyaspartylhydrazide (PAHy) as a polymeric component and various amounts of two P-CD derivatives. In particular, by reaction of PAHy with beta-CD monoaldehyde, samples named as A(1), A(2) and A(3), bearing, respectively, 4.0, 7.5 and 10.7 mol% of beta-CDs were obtained. The reaction of PAHy with 6-[aminoethyl(4'-carboxybutanamide)]-beta-CD afforded samples named as B-1 and B-2, bearing, respectively, 1.8 and 2.6 mol% of beta-CDs linked to the polymer. The occurrence of the conjugation reactions as well as the evaluation of the amount of oligosaccharides conjugated to the polymeric backbone were confirmed by FT-IR, H-1 NMR, DSC, SEC analyses and viscosimetric measurements. Molecular weight values obtained by SEC analysis were in good agreement with the theoretical increase of molecular weight of PAHy due to the beta-CD moieties linked to the polymeric backbone. Fluorescence studies on the conjugate A(3) evidenced an interaction of a probe molecule with beta-CDs linked to PAHy greater than that found with beta-CDs alone and even in both cases the formation of a 1:1 host-guest complex occurs. (c) 2006 Elsevier Ltd. All rights reserved.