Computational and experimental approaches to develop minocycline imprinted hydrogels and determination of their drug release performance

The main purpose of this thesis is to produce new formulations for contact lens synthesis which have a wide user group nowadays and that are used in the correction of visual defects and to develop suitable hydrogels for contact lenses that are featured of drug release in the treatment of chronic eye diseases such as eye pressure, xerophthalmia, and corneal neovascularization. Contact lenses are most commonly known as optical instruments that are used for cosmetic or therapeutic purposes to eliminate visual disorders. Contact lenses in today's world are made of hydrogel materials, and their soft structure provides ease of use. Biocompatibility of hydrogels with other biomaterials are higher because of their high-water content and chemical properties. Besides the contact lenses; controlled drug delivery systems, wound dressings, regenerative tissue scaffolds, organ linings, membranes with biosensor, microfluidic valves, and absorbents are set a good example for other hydrogel applications. In this study, hydrogel syntheses with high biocompatibility that can be used in contact lens applications are performed. According to the recent studies, newly developed contact lenses are planned to use in the treatment of various diseases. In this study, drug release characteristics of drug loaded hydrogel by using absorption and imprinting methods were investigated. In this study, molecular imprinting method was used to produce hydrogels with controlled drug delivery characteristics. In this study, the minocycline molecule was selected as the target molecule to be imprinted. A computerized calculation method was used in order to select suitable monomers for the synthesis of hydrogels carrying drug-delivery characteristic. By the help of molecular simulation method, the interactions of expensive and rare monomers and drug molecules are calculated, then appropriate monomer is selected. Molecular dynamic (MD) method was used in the molecular simulation stage. Functional monomers that may be selected for use in the synthesis of hydrogels include acrylic acid (AA), methacrylic acid, itaconic acid, 1 N ethyl acryl amide, 1 N isopropyl acryl amide, and hydroxymethyl acryl amide. MD calculations were done with the Materials Studio 5 Forcite module. The total simulation period is 5 nanoseconds. As a result of MD studies, it is clearly seen that itaconic acid and hydroxyethyl acrylamide monomers have the best interactivity with the minocycline molecule. The effect on the interaction between the monomer-mold molecule on the prepolymerization step of the cross-linking ratio was investigated by MD studies. In this stage of the study, experimentally applied monomer ratios were inserted into the simulation box and the cross linker - minocycline and functional monomer - interactions were investigated and compared with the experimental results. MD simulations have been conducted in the previously specified conditions. In the experimental part of the study, minocycline-printed and non-imprinted hydrogels were synthesized and then the effect of cross-linking ratio on the molecular imprinting method was investigated. Hydroxyethyl methacrylate (HEMA) was used as the main chain in the hydrogel synthesis, acrylic acid (AA) was used as the functional monomer, and ethylene glycol dimethacrylate (EGDMA) was used as the cross-linking agent. 2,2'-azobis (2,4-dimethyl-pentanenitrile) (Vazo52) was selected as the thermal initiator. It is imprinted to the minocycline polymer matrix as the mold molecule. Structural characterization of the synthesized hydrogels was conducted by Fourier transformed infrared (FT-IR) spectroscopy. According to FT-IR results, hydrogel synthesis was completed successfully. The swelling behaviors of imprinted and non-imprinted hydrogels were carried out at their loading and release temperatures of 4 °C and 37 °C. When the swelling behavior of hydrogels is investigated, it is clearly seen that temperature has no effect. Differential scanning calorimetry (DSC) was used for the thermal characterization of the synthesized hydrogels. Controlled drug delivery behavior of synthesized and characterized hydrogels are investigated. The drug loading capacities of the synthesized hydrogels were measured at 4 °C and the drug release performance was tested at 37 °C in 0.9% NaCl solution (saline solution) in order to apply the body image. The mechanism behind these findings was investigated by MD studies. Accordingly, in systems containing 2% and 3% EGDMA, the frequency and intensity of the interaction between AA acid and drug is higher than 1% EGDMA studies. According to the obtained loading and release data, hydrogel molecular imprinting properties with the ratio of 2% and 3% EGDMA are shown. In this ratio, the imprinting factor (IF) of the hydrogel that contains the EGDMA is greater than 1 and the drug release performance is higher than the non-imprinted hydrogel which contains 2% and 3% EGDMA.