Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability

Abstract

The influence of the proportion of acrylamidomethyl-γ-cyclodextrin (γ-CD-NMA) on loading and release of the hydrophobic triamcinolone acetonide (TA) and the hydrophilic propranolol (PR) by acrylic acid hydrogels was evaluated. γ-CD-NMA was synthesized by condensation of γ-cyclodextrin (γ-CD) with N-(hydroxymethyl) acrylamide. Hydrogels were prepared with γ-CD-NMA and sodium acrylate (3 M or 4 M), using N, N′-methylen(bisacrylamide) (BIS) as cross-linker, by free radical polymerization into glass moulds of 2 mm wide and were cut as discs (10 mm diameter). γ-CD-NMA did not modify the pH-dependent swelling of the hydrogels, but significantly increased the swelling degree in the 40:60 ethanol:water, medium in which TA can be dissolved. Hydrogels prepared with γ-CD-NMA above 5% (w/w of total monomers) showed a remarkably higher capacity to load TA, e.g., 33 mg/g dry hydrogel versus 0.6 mg/g dry hydrogel without γ-CD-NMA. This is explained by the formation of 1:1 inclusion complexes of TA with γ-CD mers that overcomes the lack of interactions with the acrylic groups of the network. The release of TA in water, 0.1 N HCl, or pH 6.8 phosphate buffer was sustained for at least 24 h, whatever the pH and the composition of the medium used. In contrast, loading of PR from the water solutions was greater for hydrogels prepared with 3 M acrylate than with 4 M acrylate, irrespective to their content in γ-CD-NMA, and in less than 2 h ca. 80% PR was released. The lower affinity of PR for the γ-CD cavities, compared to the strong intensity of the electrostatic interactions with the acrylic acid groups, explains why the incorporation of γ-CD-NMA did not increased the loading and control release capacity of the hydrogels of this hydrophilic drug. In summary, the copolymerisation of CD with acrylic monomers can provide highly hydrophilic pH-sensitive networks which load large amounts of hydrophobic drugs and release them in a sustained way.