Dexamethasone-21 phosphate loading and release from ph-sensitive copolymers of 2-hydroxyethyl methacrylate and 2-(diisopropylamino)ethyl methacrylate

Abstract

Smart polymerslike pH-sensitive systems can improve the pharmacological treatment ofdiseases. Topical application is perhaps the most typical treatment practice inophthalmic therapies, however it is inefficient and sometimes produces sideeffects. A possibility to improve drug residence time and bioavailability isthe use of a pH-sensitive hydrogel as a vehicle to control the drug delivery.In this work the behavior of copolymers containing 2-hydroxyethyl methacrylate(HEMA) with different proportions of 2-(diisopropylamino)ethyl methacrylate(DPA) and different amounts of cross-linker agent, ethylene glycoldimethacrylate (EGDMA) are evaluated as drugdelivery systems for ophthalmic therapies. Drug load and release studies atdifferent pH values were evaluated using dexamethasone-21 phosphate (DXP) as amodel drug. The interaction between the polymer matrix and the drug was studiedby IR spectroscopy (FTIR), and drug distribution and film morphology atdifferent pH values were studied by scanning electron microscopy (SEM). Theresults show that the loading of DXP increases with DPA content andcrosslinking degree. Also the incorporation of DXP into the matrix depends onthe medium pH and increase at basic pH. SEM images show important morphologicalchanges when varying the medium pH and it can be seen the presence of the DXPloading in the polymer matrix. FTIR spectra of copolymers show an interactionbetween the drug and the polymer matrix through the shifting of the carbonylstretching band. The release of DXP from copolymers of HEMA and DPA issensitive to small pH variations in the range of 7.00 and 7.80. Kineticsreleases shows case-II or anomalous diffusion behavior depending on theHEMA/DPA ratio. At medium ocular pH (7.40) the exponents values (n)obtained for the hydrogels containing 10 wt. % of DPA are close to 1.0,suggesting a case-II transport and for hydrogels containing 30 wt. % of DPA then values are between 0.5 and 1 indicating an anomalous behavior.