Computational and experimental approaches to develop doxycycline imprinted hydrogels for contact lenses

The aim of this thesis is to develop drug delivery hydrogels for contact lens applications which are used as therapeutic agents for cronic diseases such as high eye pressure, cornea neovascularization, eye dryness etc. Contact lenses are optical instruments which are used for elimination of visual defect or cosmetical and therapeutical purposes. Nowadays, contact lenses are made by hydrogel materials which has high water cater content and biocompatibility due to chemical properties. In the studies, newly developed contact lenses are intended to be used for the treatment of ophthalmological diseases. Drug molecules can be loaded to the contact lenses with various methods such as soaking, molecular imprinting or loading to the polymer matrices with colloidal nonoparticles. In this study, doxycycline hyclate molecules are loaded to the hydrogels by soaking and molecular imprinting methods. In this thesis, molecular imprinting method was preferred to synthesize controlled drug released hydrogels. Imprinted polymers which have special cavities belonged to target molecules, are highly selective against to targets. In this study, doxycycline hyclate molecule is choosen as target molecule which is imprinted to the hydrogel matrices. Doxycycline hyclate which is broad spectrum antibiotic, has not been used as template molecule for contact lens applications in literature. In this study, computational methods were used to select suitable monomers for doxycycline imprinted hydrogel synthesis. In molecular simulation step, quantum mechanics, molecular mechanics and molecular dynamic techniques were used. By using quantum mechanics and molecular mechanics, binding interactions between functional monomers and doxycycline molecule were calculated. Quantum mechanics calculations were carried out with Gaussian 09 and SYBYL-X software was used for molecular mechanics studies. Molecular dynamic studies of functional monomer-doxycycline systems were carried with Material Studio 5.0. Also, the effects of crosslinker on prepolymerization step were investigated with molecular dynamic studies. In this step, interactions of crosslinker-doxycycline-functional monomer were studied to simulate experimental conditions. These results were compared with experimental results. In the experimental part, in order to determine crosslinker effect on drug release performance, doxycycline hyclate imprinted and non-imprinted hydrogels were prepared in various crosslinker ratios (1, 1.5, 2, 3 % mole EGDMA). Imprinted and non-imprinted hydrogels were syntesized by free radical polymerization. Acrylic acid was choosen as functional monomer for polymer synthesis. All hydrogels were characterized by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Also, swelling behaviors of hydrogels were investigated. Doxycycline loading and release performances of both imprinted and non-imprinted hydrogels were investigated. Based on release performances, drug release kinetic profiles were evaluated. According to loading and release performances, doxycycline imprinted hydrogel sample which include 3% mole EGDMA, has higher imprinting factor and more controlled drug release performance compared to other hydrogels.