A chorioallantoic membrane model for the determination of anti-angiogenic effects of imatinib.

Tumor angiogenesis is of major importance in the growth and metastasis of solid tumors, and the development of anti-angiogenic treatment strategies is thus a relevant option in oncology. The chorioallantoic membrane (CAM) model is a rapid and simple alternative to in vivo studies for the evaluation of anti-angiogenic compounds, thus allowing to reduce animal experiments and, upon establishment of robust and reproducible procedures, to more efficiently and objectively assess the anti-angiogenic efficacy of a given drug. In this paper, we compare two different methods for tumor establishment on a CAM model: (i) a Murine Urothelial Carcinoma (MB49) cell suspension mixed with Matrigel and (ii) an MB49 cell suspension absorbed in Gelfoam gelatin sponges. Based on the applicability of both methods for implant formation, we identify Gelfoam gelatin sponges as superior due to better attachment of the tumors on the membrane surface. For the precise quantitation of tumor xenograft growth and angiogenesis, we furthermore establish in this paper the electronic capturing of the xenografts and the computer-based analysis of the microscopic CAM images in order to determine the number of intersecting vessels and to measure vessel diameters. Beyond its direct effect on tumor cells by inhibiting the tyrosine kinase domain of the abl gene, imatinib has been reported to reduce the Bcr-Abl-mediated secretion of the angiogenesis factor VEGF and hence to interfere with angiogenesis. To test our CAM model for its ability to monitor anti-angiogenic effects, Gelfoam gelatin sponge-based tumor implants were treated by topical application of imatinib at various concentrations. Besides anti-tumor effects, we observed an inhibition of angiogenesis as determined by the number or total diameter of intersecting vessels. We also demonstrate that the calculation of the "blood vessel index" (vessel total diameter/tumor circumference) in our model allows to assess anti-angiogenic effects of imatinib independently of tumor growth inhibition. We conclude that our CAM assay and computer-based analysis represent a useful in vitro technique for the rapid assessment of anti-angiogenic effects of various agents.

Archaebacterial tetraetherlipid liposomes.

Liposomes are widely investigated for their applicability as drug delivery systems. However, the unstable liposomal constitution is one of the greatest limitations, because the liposomes undergo fast elimination after application to the human body. In the presented study, novel archeal lipids were used to prepare liposomal formulations which were tested for their stability at elevated temperatures, at different pH-values and after heat sterilization.

Utilising atomic force microscopy for the characterisation of nanoscale drug delivery systems.

The introduction of atomic force microscopy (AFM) techniques has revolutionised our ability to characterise colloidal objects. AFM allows the visualisation of samples with sub-nanometre resolution in three dimensions in atmospheric or submerged conditions. Nanomedical research is increasingly focused on the design, characterisation and delivery of nano-sized drug carriers such as nanoparticles, liposomes and polyplexes, and this review aims to highlight the scope and advantages of AFM in this area. A significant amount of work has been carried out in drug delivery system (DDS) research in recent years using a large variety of techniques. The use of AFM has enabled us to directly observe very small objects without the need of a cumbersome and potentially contaminating sample preparation. Thus, nanoscale DDS can be investigated in a controlled environment without the necessity of staining or drying. Moreover, intermittent contact mode AFM allows the investigation of soft samples with minimal sample alteration; phase imaging allows accessing information beyond the sample's topography and also differentiating between different materials, and force spectroscopy experiments help us to understand the intrinsic structure of DDS by recording the elastic or adhesion behaviour of particles. Hence, AFM enables us accessing information which is hardly available by other experimental techniques. It has provided invaluable information about physicochemical properties and helped to shed light on the area of nanoscale drug delivery and will, with more and more sophisticated equipment becoming available, continue to add to our understanding of the behaviour of nanoscale DDS in the future.