Drug-containing cross-linked hyaluronic acid systems

Traditional drug delivery systems have some disadvantages in terms of effective treatment. New generation drug delivery systems eliminate these disadvantages and open the door to personalised treatments by increasing the bioavailability of drugs and patient compliance. Hyaluronic acid-based hydrogel drug delivery systems stand out as a preferred platform in drug delivery systems due to their properties. Hyaluronic acid is used in many biomedical applications thanks to its water absorption capacity and hydrophilic structure with high biocompatibility. Thanks to the functional groups on its structure, it can be easily modified and its stability against the enzyme hyaluronidase in the body can be increased. Cross-linked hyaluronic acid hydrogel fillers can be used in many biomedical fields thanks to their high mechanical properties. In this thesis, in-vitro and in-vivo degradation studies were carried out with various drug groups which are enzyme inhibitors in order to increase the stability of cross-linked hyaluronic acid. Firstly, crosslinked hydrogel fillers were synthesised and mixed with selected hyaluronidase inhibitors. The rheological properties, which are critical for the applicability of hydrogel fillers, were first investigated and FTIR, NMR and SEM analyses were performed. In-vitro degradation studies of hydrogel fillers were carried out and their resistance to enzyme was investigated. Cell studies were carried out and viability results were observed. Then, the drug release kinetics of the hydrogel fillers containing the appropriate drug groups were studied. After chemical characterisation, cell studies and in-vitro release study, AHM0,6 hydrogel filler was found suitable for in-vivo experiment. As a result, none of the drug-containing hydrogel fillers showed toxic effects. As a result of in-vitro and in-vivo studies, it was observed that AHM0,6 hydrogel group was the most resistant to degradation by maintaining the mechanical properties of the hydrogel structure. In this study, drug-containing hyaluronic acid hydrogel fillers were prevented from degradation against the enzyme in the body and a longer lasting effect was achieved. It opens new doors to the applicability of hyaluronic acid-based drug delivery systems used in personalized treatments. Keywords: Hyaluronic acid, Drug delivery system, Cross-linked hyaluronic acid, D Enzyme inhibitor, Biomaterials, Medical Device