Just Keep Rolling?—An Encompassing Review towards Accelerated Vaccine Product Life Cycles

In light of the recent pandemic, several COVID-19 vaccines were developed, tested and approved in a very short time, a process that otherwise takes many years. Above all, these efforts have also unmistakably revealed the capacity limits and potential for improvement in vaccine production. This review aims to emphasize recent approaches for the targeted rapid adaptation and production of vaccines from an interdisciplinary, multifaceted perspective. Using research from the literature, stakeholder analysis and a value proposition canvas, we reviewed technological innovations on the pharmacological level, formulation, validation and resilient vaccine production to supply bottlenecks and logistic networks. We identified four main drivers to accelerate the vaccine product life cycle: computerized candidate screening, modular production, digitized quality management and a resilient business model with corresponding transparent supply chains. In summary, the results presented here can serve as a guide and implementation tool for flexible, scalable vaccine production to swiftly respond to pandemic situations in the future

Analysis of Trajectories for Targeting of Magnetic Nanoparticles in Blood Vessels

The technique of magnetic drug targeting deals with binding drugs or genetic material to superparamagnetic nanoparticles and accumulating these complexes via an external magnetic field in a target region. For a successful approach, it is necessary to know the required magnetic setup as well as the physical properties of the complexes. With the help of computational methods, the complex accumulation and behavior can be predicted. We present a model for vascular targeting with a full three-dimensional analysis of the magnetic and fluidic forces and a subsequent evaluation of the resulting trajectories of the complexes. These trajectories were calculated with respect to the physiological boundary conditions, the magnetic properties of both the external field and the particles as well as the hydrodynamics of the fluid. We paid special regard to modeling input parameters like flow velocity as well as the distribution functions of the hydrodynamic size and magnetic moment of the nanoparticle complexes. We are able to estimate the amount of complexes, as well as the spatial distribution of those complexes. Additionally, we examine the development of the trapping rate for multiple passages of the complexes and compare the influence of several input parameters. Finally, we provide experimental data of an <i>ex vivo</i> flow-loop system which serves as a model for large vessel targeting. In this model, we achieve a deposition of lentivirus/magnetic nanoparticle complexes in a murine aorta and compare our simulation with the experimental results gained by a non-heme-iron assay

Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets

Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation at predilection sites. Also surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function and restenosis. In the current study we have examined a potentially curative approach by radially symmetric re-endothelialization of vessels after their mechanical denudation. For this purpose a combination of nanotechnology with gene and cell therapy was applied to site-specifically re-endothelialize and restore vascular function. We have used complexes of lentiviral vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded and eNOS-overexpressing cells were magnetic, and by magnetic fields they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions. We demonstrate that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in eNOS^–/– mice <i>ex</i> and <i>in vivo</i>. Thus, the combination of MNP-based gene and cell therapy with custom-made magnetic fields enables circumferential re-endothelialization of vessels and improvement of vascular function