Towards a simple in vitro surface chemistry pre-screening method for nanoparticles to be used for drug delivery to solid tumours.

An efficient nanoparticulate drug carrier intended for chemotherapy based on intravenous administration must exhibit a long enough blood circulation time, a good penetrability into the tumour volume, as well as an efficient uptake by cancer cells. Limiting factors for the therapeutic outcome in vivo are recognition of the nanoparticles as foreign objects, which triggers nanoparticle uptake by defence organs rich in macrophages, e.g. liver and spleen, on the time-scale of accumulation and uptake in/by the tumour. However, the development of nanomedicine towards efficient nanoparticle-based delivery to solid tumours is hampered by the lack of simple, reproducible, cheap, and predictive means for early identification of promising nanoparticle formulations. The surface chemistry of nanoparticles is known to be the most important determinant for the biological fate of nanoparticles, as it influences the extent of serum protein adsorption, and also the relative composition of the protein corona. Here we preliminarily evaluate an extremely simple screening method for nanoparticle surface chemistry pre-optimization based on nanoparticle uptake in vitro by PC-3 cancer cells and THP-1 macrophages. Only when both selectivity for the cancer cells as well as the extent of nanoparticle uptake are taken into consideration do the in vitro results mirror literature results obtained for small animal models. Furthermore, although not investigated here, the screening method does also lend itself to the study of actively targeted nanoparticles.

Safety studies with the oral rabies virus vaccine strain SPBN GASGAS in the small Indian mongoose (Herpestes auropunctatus).

BACKGROUND: Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. RESULTS: The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. CONCLUSION: The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose.