Freisetzungsverhalten von unterschiedlich hydrophil/hydrophoben Modellsubstanzen aus Poly-(D,L-lactid)- und Poly-(D,L-lactid)-co-PEO-co-poly-(D,L-lactid)-Mikrosphären und pharmazeutische Anwendungen

摘要

Within the scope of this dissertation, the release behaviour of different model substances and drugs from degradable poly-(D,L-lactide) (PDLLA) and poly-(D,L-lactide)-co-PEO-co-poly-(D,L-lactide) (ABA) microspheres as well as poly-(D,L-lactide-co-TMC)(90:10) nanospheres in PBS-buffer are characterised. To investigate the release behaviour, three different hydrophilic/hydrophobic benzophenone based model substances were chosen; 2,2’-dihydroxy-4,4’-dimethoxy-benzophenone-5,5’-disodium-sulfonate (Uvinul DS-49™), 2,2’,4,4’-tetrahydroxy-benzophenone (Uvinul D-50™) and 2-hydroxy-4-methoxy-benzophenone (Uvinul M-40™). The ABA-triblock copolymer was synthesized by ring opening polymerisation of lactide in the presence of polyethyleneoxide (PEO, 2000) as an initiator and tin(II)-2-ethylhexanoate as a catalyst. PDLLA and ABA-triblockcopolymer microspheres were made according to the o/w-solvent-evaporation method. The three model substances DS-49, D-50 and M-40 were incorporated with a theoretical loading of 9, 13 and 17 weight% respectively. The resultant microspheres were, depending on the particle size distribution, separated into two or three particle fractions in the range of 100-300µm, 300-710µm and if available 710-1000µm. The release behaviour was investigated depending on the particle size, the loading, the model substance and the polymeric matrix. Furthermore, the degradation behaviour of the 300-710µm ranged PDLLA- and ABA-microspheres was investigated depending on the qualitative and quantitative loading for three weeks. A 100-day value was determined additionally to estimate tendencies. In doing so, a dependency of the incorporated substance to the degradation behaviour of the polymer can be observed. Another part of this work deals with the production of a drug release system for use in ophthalmology. To treat proliferative vitreoretinopathy (PVR) a drug release system is required to prevent an undesired proliferation of retinal pigment epithel cells (RPE cells) on the retina. Ascorbic acid loaded PDLLA microspheres were made according to the o/w-solvent-evaporation method. These spheres were tested in an in vitro drug release experiment. Furthermore the incorporation of nanospheres into an e-PTFE foil covered stent for use in angioplasty is described in this work. Spherical nanoparticles made of poly(D,L lactide-co-TMC) (90:10) were designed in different size-distributions via the o/w solvent evaporation process. The nanosphere suspensions were pressed with pressure through an e-PTFE covered stent to obtain a foil loaded with nanoparticles. The release behaviour of the dexamethasone or paclitaxel loaded nanospheres incorporated in the stent was investigated in an in vitro experiment.