Functionalization of acrylic hydrogels with alpha-, beta- or gamma-cyclodextrin modulates protein adsorption and antifungal delivery.

Poly(hydroxyethyl methacrylate) (pHEMA) hydrogels were functionalized with pendant alpha-, beta- and gamma-cyclodextrins (CD) with the aim of improving the biocompatibility and increasing the ability to host drug molecules. Pendant alpha-, beta- and gamma-CDs did not affect swelling of the hydrogels but slightly decreased the water contact angle. Protein deposition was notably dependent on the nature of the CD, due to their different affinities for hydrophobic moieties of proteins. Lysozyme and albumin sorption was hindered by gamma-CD. Functionalization with beta-CD also reduced protein sorption, although less so, while alpha-CD decreased lysozyme deposition but enhanced albumin sorption compared with control pHEMA hydrogels. Loading of the hydrogels with miconazole was carried out by immersion in drug suspension followed by autoclaving. Functionalization with gamma-CD doubled the affinity of the network for the drug and resulted in the highest amount loaded (up to 170 mgg(-1)). Sustained delivery was observed for several days. Some miconazole-loaded hydrogels completely prevented Candida albicans biofilm formation as assayed in an in vitro microbiological test.

Soft contact lenses functionalized with pendant cyclodextrins for controlled drug delivery.

The aim of this work was to develop acrylic hydrogels with high proportions of cyclodextrins maintaining the mechanical properties and the biocompatibility of the starting hydrogels, but notably improving their ability to load drugs and to control their release rate. Poly(hydroxyethylmethacrylate) hydrogels were prepared by copolymerization with glycidyl methacrylate (GMA) at various proportions and then beta-cyclodextrin (betaCD) was grafted to the network by reaction with the glycidyl groups under mild conditions. This led to networks in which the betaCDs form no part of the structural chains but they are hanging on 2-3 ether bonds through the hydroxyl groups. The pendant betaCDs did not modify the light transmittance, glass transition temperature, swelling degree, viscoelasticity, oxygen permeability, or surface contact angle of the hydrogels, but decreased their friction coefficient by 50% and improved diclofenac loading by 1300% and enhanced drug affinity 15-fold. The hydrogels were able to prevent drug leakage to a common conservation liquid for soft contact lenses (SCLs) and to sustain drug delivery in lacrimal fluid for two weeks. To summarize, the hydrogels with pendant betaCDs are particularly useful for the development of cytocompatible medicated implants or biomedical devices, such as drug-loaded SCLs.

Poly(hydroxyethyl methacrylate-co-methacrylated-beta-cyclodextrin) hydrogels: synthesis, cytocompatibility, mechanical properties and drug loading/release properties.

Copolymerization of hydroxyethyl methacrylate (HEMA) with a methacrylated-derivative of beta-cyclodextrin (beta-CD) was evaluated as a way to obtain hydrogels with tunable mechanical and drug loading and release properties, particularly for preparing medicated soft contact lenses. A fully methacrylated beta-CD monomer was synthesized and added to the HEMA and cross-linker solution at concentrations ranging from 0.042 to 0.333 g ml(-1) (i.e. 0.23-1.82 mol.%). Thermal polymerization led to transparent hydrogels with a degree of conversion above 74%, which showed a high cytocompatibility and did not induce macrophage response. The greater the content in methacrylated beta-CD was, the higher the glass transition temperature, the lower the degree of swelling and free water proportion, and the greater the storage and loss moduli of the swollen disks. These findings are directly related to the increase in the degree of cross-linking caused by the methacrylated beta-CD. Loading studies were carried out with hydrocortisone and acetazolamide, both able to form complexes with CDs in water and in lacrimal fluid. Hydrocortisone loading progressively decreased as the content in methacrylated beta-CD rose due to a decrease in the volume of aqueous phase of the hydrogel. Acetazolamide loading showed a maximum for an intermediate content in beta-CD (0.125-0.167 g ml(-1)) owing to a balance between complexation with beta-CD and hydrogel mesh size. The hydrogels sustained drug delivery for several days, the acetazolamide release rate being dependent on the beta-CD content. An adequate selection of the content in beta-CD enables pHEMA-co-beta-CD hydrogels suitable for specific biomedical applications to be obtained.