Nanoyapılı aerojellerin ilaç taşıyıcı sistemi olarak incelenmesi

Over the past few years, nanoporous aerogels have shown a great promise as drug delivery vehicles. In this study, inorganic and organic aerogels such as silica aerogel and alginate aerogel were investigated as drug delivery systems. Moreover, a novel layered material consisting of these two distinct aerogels was prepared for the first time by encapsulating a silica aerogel with an alginate aerogel layer. To investigate aerogels as drug delivery vehicles, different methods are utilized to load drugs into them such as the addition of the drug to the reaction mixture in one of the steps before the gel formation or by supercritical deposition to the aerogels. These techniques have disadvantages such as low solubility of pharmaceutical compounds in scCO2 and possible reactions of pharmaceutical compounds with reactants used to form gels. An alternative technique is to load the drug after gel formation by contacting the gel with a solution of the drug. The drug diffuses into the liquid inside the pores. When this drug-loaded gel is subjected to supercritical drying, scCO2 not only removes the solvent from the pores but also acts as an antisolvent, which causes the precipitation of the drug in the pores of the aerogel. This is similar to the gas antisolvent crystallization (GAS) process but in this case the process takes place inside the pores. In this study, this technique was used to load paracetamol into silica and alginate aerogels with densities ranging 0.13 to 0.15 g/cm3 and 0.055 to 0.062 g/cm3 respectively. The initial concentration of the paracetamol-ethanol solution ranged from 0.25 M to 0.8 M. The factors affecting the amount and distribution of the drug inside the aerogel matrix were investigated. The Attenuated Total Reflectance (ATR) results indicated that the paracetamol diffused inside of the aerogel and X-ray Diffraction (XRD) analysis demonstrated that the paracetamol was in crystalline form. It was possible to control loading by changing the concentration of the drug in the contacting solution and also by changing the pore volume of the alcogel matrix which in turn depended on the reactant concentrations. Moreover, the process enabled very high amount of loadings such as 40 wt. % for silica aerogels and 75 wt.% for alginate aerogels compared to conventional systems and also offers an advantage for aerogels as it combines two processes such as drying and loading in a single one reducing the time and the operating expenses. On the other hand, diffusion of paracetamol inside the pores was also theoretically modeled by solving partial differential equations. Experimental paracetamol uptake was shown to be in good agreement with the model predictions without any adjustable parameters. Finally, the release of paracetamol from loaded aerogel supports in PBS buffer was investigated showing the promise of these materials as drug delivery vehicles. It was shown that native aerogels could be used as carriers for fast acting medications whereas the hybrid aerogel was suitable to achieve a retarded release profile. A mathematical model was also developed to describe the release kinetics of paracetamol from alginate aerogels comprising the swelling of the aerogel matrix, the dissolution of the drug into the pore liquid followed by its diffusion from the pores into the surrounding medium. The inclusion of these physical phenomena in the mathematical model had greatly reduced the deviations from the experimental data and resulted in good model predictions.