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 β-cyclodextrins (β-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 α,β-polyaspartylhydrazide (PAHy) as a polymeric component and various amounts of two β-CD derivatives. In particular, by reaction of PAHy with β-CD monoaldehyde, samples named as A1, A2 and A3, bearing, respectively, 4.0, 7.5 and 10.7 mol% of β-CDs were obtained. The reaction of PAHy with 6-[aminoethyl(4′-carboxybutanamide)]-β-CD afforded samples named as B1 and B2, bearing, respectively, 1.8 and 2.6 mol% of β-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, 1H 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 β-CD moieties linked to the polymeric backbone. Fluorescence studies on the conjugate A3 evidenced an interaction of a probe molecule with β-CDs linked to PAHy greater than that found with β-CDs alone and even in both cases the formation of a 1:1 host–guest complex occurs.