| Abstract |
Bisphosphonates (BPs) constitute a class of drugs that are used to mitigate osteoporosis and other bone-related diseases. BPs comprise a more stable chemical analog of pyrophosphoric acid, which participates in the regulation process of biological metabolic path of calcification. Some drawbacks of these BP drugs are their limited bioavailability, poor biocompatibility and fast excretion that lead to a plethora of side effects. Hence, the design and fabrication of smart drug delivery systems is necessary, in order to achieve effective treatment. Laponites ® constitute a class of phyllosilicate inorganic minerals, which are insoluble in water, but can undergo extensive hydration to form highly thixotropic gels. Thixotropy is the ability of a colloidal dispersionto transit from gel-to-sol, when it is shaken or shear-stressed, in a reversible way. Laponite® hydrogels are non-toxic and biocompatible. As a result, they are broadly used in cosmetics and pharmaceutical products to enhance their organoleptic properties. In addition, they possess a unique “house-of-cards” structure in water dispersions and display void spaces within the clay’s particles and shear thinning capacity, which render them suitable as drug delivery systems for injectable drugs. In this way, the treatments can be conducted in a more targeted fashion, reducing the side effects and enhancing the treatment’s effectiveness. The scope of the present Master’s Thesis was focused on different formulations of Laponite® XL-21 XR (F18Mg16Na10O66Si27) in order to fabricate stable hydrogels, loaded with the anti osteoporosis drug Etidronic acid (CH3C(OH)(PO3H2)2), and on the evaluation of the controlled release profile of the drug. Etidronic acid was effectively loaded on the Laponite® hydrogels, because it can interact electrostatically or via hydrogen-bonds with the hydrogel’s silicatic network. Subsequently, controlled release studies were conducted in artificial fluids that mimic the human stomach (pH 1.3) or the human blood (pH 7.4). Drug-loaded Laponite® hydrogels were prepared and were allowed to mature. Subsequently, an aqueous medium of appropriate pH was carefully added as a supernatant fluid phase. As a result, the active drug was gradually released to the supernatant phase and the quantification of the initial release rate of the active drug was realized by 1H Nuclear Magnetic Resonance spectroscopy. The raw data (peak integration vs. time) were converted to release diagrams (% drug release vs. time). Different variables have been studied in order to fully understand the behavior of these drug-loaded hydrogel systems and their release profiles. Some factors that appeared to influence the release profiles were: 12 (a) the composition of the gel or the supernatant, (b) the pΗ of the supernatant, and (c) the system’s temperature. In order to gain a deeper insight in the hydrogel’s network, leaching studies of inherent Mg2+ and silicate ions were carried out. Lastly, attempts of grafting the clay’s surface were conducted using the organosilanes APTES (3-aminopropyl)triethoxysilane) and TESPSA (3-(triethoxysilyl)propylsuccinic anhydride) in order to produce silane-grafted derivatives. The approach was based on the concept of adding different functional groups that can change the overall charge of the exposed nanoparticle surface. This is expected to influence the interactions between Etidronic acid and the hydrogel matrix, thus altering the release profile of the drug.
|
Collections
