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.
dos Santos
Jose-Fernando Rosa
JF
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782-Santiago de Compostela, Spain.
Couceiro
Ramiro
R
Concheiro
Angel
A
Torres-Labandeira
Juan-Jose
JJ
Alvarez-Lorenzo
Carmen
C
D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D006854:Hydrocortisone / Q000494:pharmacology; D020100:Hydrogels / Q000138:chemical synthesis*; D008689:Methacrylates / Q000138:chemical synthesis*; D051379:Mice; D011409:Propylene Glycols / Q000138:chemical synthesis*; D012212:Rheology; D012995:Solubility / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water; D047392:beta-Cyclodextrins / Q000138:chemical synthesis*
D001672:Biocompatible Materials; D020100:Hydrogels; D008689:Methacrylates; D011409:Propylene Glycols; D047392:beta-Cyclodextrins; C507884:poly(beta-cyclodextrin); D014867:Water; C005044:hydroxyethyl methacrylate; C031215:betadex; D000086:Acetazolamide; D006854:Hydrocortisone