Simvastatin için Kontrollü İlaç Salım Sisteminin Geliştirilmesi

Abstract

In this study, poly(2-hydroxyethyl methacrylate-N-methacryloyl-L-tryptophan methyl ester) cryogel membranes were synthesized at different concentrations using the molecular imprinting technique (MIT) for controlled release of simvastatin. Synthesis of simvastatin imprinted (MIP) and non-imprinted (NIP) cryogel membranes was carried out at -20 °C for 24 hours. Cryogel membranes were prepared with a diameter of 10 mm and a thickness of 1.0 mm. Cryogel membranes containing simvastatin at different concentrations (0.5 mg, 0.75 mg and 1 mg) were prepared as MIP-I, MIP-II and MIP-III, respectively, and in order to evaluate the effect of the drug loading amount on the release of each group of membranes, 0.05 mg/mL, 0.25 mg/mL and 0.5 mg/mL simvastatin solutions were prepared and the loading process was performed. Swelling tests were performed to evaluate the swelling properties and crosslinker ratios of the prepared membranes and it was determined that the template molecule had an enhancing effect on both swelling and macropore ratio due to its hydrophilic nature. Fourier transform infrared (FTIR) spectroscopy was applied to determine the functional groups present in the cryogel matrix and to evaluate the degree of chemical change that occurred during the synthesis, peaks belonging to OH stretching of aromatic hydroxy and asymmetric etheric groups were found in the simvastatin spectrum at 3,551 cm-1 and 870 cm-1, confirming the intact structure of simvastatin in the membranes. By 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test, cell viability in cryogel membranes was reported as 41 ± 2.71, 54 ± 1.38, 60 ± 3.88, 53 ± 1.04 after 24 h loading with simvastatin, respectively. X-Ray Diffraction (XRD) method was used to determine the crystal structure of the materials and simvastatin exhibited high crystallinity due to sharp peaks (10.98°, 15.70°, 16.62°, 17.32°, 17.82°, 18.88°, 19.50°, 22.12° and 22.66°) at the diffraction angle (2θ), thus simvastatin was found to be in crystalline form. As a result of the study, the best release was observed when MIP-III cryogel membranes were loaded with 0.5 mg/mL simvstatin solution at 37 °C, 10:1 crosslinker ratio (pH 7.4). For the sterility test of cryogel membranes, nutrient agar and nutrient broth were used and membranes were inoculated into the medium and after incubation for 2-5 days (37 °C), the medium was examined and no bacterial growth was observed. To obtain the kinetic parameters (ka, kd and KD) of this study, SIM imprinted poly(HEMA-MATrp) (MIP) and non-imprinted (NIP) surface plasmon resonance (SPR) sensors were designed. Different isotherm models were applied to determine the binding kinetic analysis and adsorption model between the SPR sensors and SIM. When the data in the concentration range of simvastatin (0.001-1 mg/mL) were evaluated, the equations (y=9.799x-0.0061) and (y=3.3314x+1.585) were obtained from the graphs, respectively. The linearity coefficient from these graphs were found to be (R2 = 0.997) and (R2 = 0.9255), respectively, indicating a 99% measurement accuracy. This study is believed to contribute to the literature by comparing the advantages of the cryogel membrane prepared using the molecular imprinting method for controlled simvastatin release.