Biodegradable polyesters for veterinary drug delivery systems: Characterization, in vitro degradation and release behavior of Oligolactides and Polytartrate

摘要

This thesis deals with the degradation and release behavior of aliphatic polyesters with special respect to the influence of oligomers on the degradation rate and the potential use of these biomaterials for the development of veterinary drug delivery systems. In Chapter 1 the animal health care market is introduced with regard to opportunities and challenges of veterinary drug delivery systems. . In the second part of this chapter biodegradable polymers used for veterinary applications are discussed with emphesis on their degradation and release properties. Current applications of biodegradable drug delivery systems in the field of reproduction control, growth promotion, vaccination and control of ectoparasites are summarized. Chapter 2 describes the synthesis and characterization of a homologous series of low molecular weight poly(D,L-lactides). The oligomers were analyzed using SEC, DSC and 1H-NMR to obtain information about their physico-chemical properties as function of average chain length. The interest was focused on the determination of the critical molecular weight for water solubility of oligomers. In addition the hydrolysis kinetic of oligomer degradation and the mechanism of ester cleavage was investigated in vitro. The effect of low molecular weight poly(D,L-lactides) on the degradation process of PLGA is reported in Chapter 3. PLGA films containing oligomers of different molecular weight in various amounts were prepared by a solvent casting technique and the degradation was monitored by SEC, WAXD, DSC and gravimetric methods. Chapter 4 describes the characterization and in vitro degradation of Poly(2,3-(1.4-diethyl tartrate)-co-2,3-isopropyliden tartrate). In Chapter 5 the influence of the degradation behavior on in vitro drug release from PTA implants is described. Effects of drug loading and implant size on release profile were studied in more detail. Chapter 6 describes the in vivo release properties of buserelin implants in dogs. By using model-independent methods such as statistical moment analysis and model-dependent methods (curve-fitting) the in vitro release profiles were compared to the in vivo performance. An attempt was made to develop different levels of in vitro-in vivo correlation for biodegradable implants.