Tomographic and Topographic Investigation of Poly-D,L-Lactide-co- Glycolide Microspheres Loaded with Prostaglandine E_2 for Extended Drug Release Applications

摘要

Polymeric, biodegradable microspheres represent a good reliable system to investigate the release of bioactive substances in both in vitro and in vivo applications. Common biomaterials for the synthesis of these microspheres are aliphatic polyesters of the poly(α-hydroxy)acids, especially poly-L-lactides (PLA) and polyglycolides (PGA) or their copolymers poly-D,L-lactide-co-glycolides (PLGA). In our own previous studies we have developed PLGA microspheres with integrated PGE_2 as model substance for a wide range of biomedical applications, especially in angiogenesis, fracture healing and cartilage repair. The synthesis is based on a binary solvent in water emulsion approach, where two different solvents are used to dissolve the active agent and the polymer, while being miscible in each other (CHCl_3, ethyl acetate). Both, the degradation of the material and the release profiles were investigated using SEM and mass spectrometry coupled with gas- or high performance liquid chromatography. SEM and AFM measurements indicated a porous structure of the microspheres but could not resolve the true three dimensional structure of the microspheres. Therefore, synchrotron radiation-based μCT (SR-μCT) investigations were performed to link the release profile to the structural design of the microspheres. As a result, we were able to cross validate the experimental data from SEM and AFM with SR-μCT, demonstrating both microporosity and nano-porosity. The polymer itself appears to consist of 200 nm - 300 nm sized particles.