Convergent click synthesis of macromolecular dendritic β-cyclodextrin derivatives as non-conventional drug carriers: Albendazole as guest model

Abstract

From a materials science perspective, herein we present the design and synthesis of six macromolecular carbohydrate derivatives, obtained by combining the native cyclic oligosaccharide βCD and dendritic poly(ester) moieties, coupled by CuAAc click reactions, in a convergent fashion. We envisioned two structural variables to promote the formation of inclusion complexes (ICs) with the anti-parasitic drug Albendazole, the degree of substitution on the βCD (mono or hepta-substitution) and the dendritic generation (from first to third). In terms of synthetic effort and cost, the mono-substituted βCD derivatives were obtained in more approachable experimental conditions in comparison to the βCD dendrimers (hepta-substituted macrocycle). The six dendritic derivatives were more soluble in water and showed better complexation capacity than native βCD. For both, mono and hepta-substituted βCD, we observed that the amount of encapsulated ABZ increases when the dendron generation increases. Interestingly, different degrees of substitution (mono and hepta) lead comparable results of ABZ complexation. In conclusion, the encapsulation performance and the consequent solubility enhancement, make these molecular containers excellent materials to positively impact the therapeutic desirability of ABZ.

Keywords: Click chemistry; Cyclodextrin; Dendrimer; Therapeutic desirability.