Central nervous system diseases are a heavy burden on society and health care systems. Hence, the delivery of drugs to the brain has gained more and more interest. The brain is protected by the blood–brain barrier (BBB), a selective barrier formed by the endothelial cells of the cerebral microvessels, which at the same time acts as a bottleneck for drug delivery by preventing the vast majority of drugs to reach the brain. To overcome this obstacle, drugs can be loaded inside nanoparticles that can carry the drug through the BBB. However, not all particles are able to cross the BBB and a multitude of factors needs to be taken into account when developing a carrier system for this purpose. Depending on the chosen pathway to cross the BBB, nanoparticle material, size and surface properties such as functionalization and charge should be tailored to fit the specific route of BBB crossing.

This commentary article conveys the views of the board of the Nanomedicine and Nanoscale Delivery Focus Group of the Controlled Release Society regarding the decision of the United States National Cancer Institute (NCI) in halting funding for the Centers of Cancer Nanotechnology Excellence (CCNEs), and the subsequent editorial articles that broadened this discussion.

Current research on wound infections is primarily conducted on animal models, which limits direct transferability of these studies to humans. Some of these limitations can be overcome by using–otherwise discarded—skin from cosmetic surgeries. Superficial wounds are induced in fresh ex vivo skin, followed by intradermal injection of Pseudomonas aeruginosa under the wound. Subsequently, the infected skin is incubated for 20 hours at 37°C and the CFU/wound are determined. Within 20 hours, the bacteria count increased from 107 to 109 bacteria per wound, while microscopy revealed a dense bacterial community in the collagen network of the upper wound layers as well as numerous bacteria scattered in the dermis. At the same time, IL-1alpha and IL-1beta amounts increased in all infected wounds, while—due to bacteria-induced cell lysis—the IL-6 and IL-8 concentrations rose only in the uninfected samples. High-dosage ciprofloxacin treatment resulted in a decisive decrease in bacteria, but consistently failed to eradicate all bacteria. The main benefits of the ex vivo wound model are the use of healthy human skin, a quantifiable bacterial infection, a measureable donor-dependent immune response and a good repeatability of the results. These properties turn the ex vivo wound model into a valuable tool to examine the mechanisms of host-pathogen interactions and to test antimicrobial agents.

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