Viral nanoparticles: Current advances in design and development.

Viral nanoparticles (VNPs) are self-assembling, adaptable delivery systems for vaccines and other therapeutic agents used in a variety of biomedical applications. The potential of viruses to invade and infect various hosts and cells renders them suitable as potential nanocarriers, possessing distinct functional characteristics, immunogenic properties, and improved biocompatibility and biodegradability. VNPs are frequently produced through precise genetic or chemical engineering, which involves adding diverse sequences or functional payloads to the capsid protein (CP). Several spherical and helical plant viruses, bacteriophages, and animal viruses are currently being used as VNPs, or non-infectious virus-like particles (VLPs). In addition to their broad use in cancer therapy, vaccine technology, diagnostics, and molecular imaging, VNPs have made important strides in the realms of tissue engineering, biosensing, and antimicrobial prophylaxis. They are also being used in energy storage cells due to their binding and piezoelectric properties. The large-scale production of VNPs for research, preclinical testing, and clinical use is fraught with difficulties, such as those relating to cost-effectiveness, scalability, and purity. Consequently, many plants- and microorganism-based platforms are being developed, and newer viruses are being explored. The goal of the current review is to provide an overview of these advances.

Brain Virome in Neurodegenerative Disorders: Insights from Transcriptomic Data Analysis.

Neurodegenerative disorders (NDs) are chronic ailments of the central nervous system that gradually deteriorate the structures and functions of neurons. The etiologies of NDs include genetic factors, aging, infections, starvation, brain trauma, and spinal cord injury, among others. However, it is unclear whether viral infections impact the prognosis of NDs or contribute to their development. Hence, we investigated the prevalence of neurotropic viruses in brain samples by using transcriptomic data. A total of 1635 viral isolates with complete genomic information was used to investigate the incidence of 18 distinct viruses across 129 data sets from healthy and ND subjects. Our findings support the evidence pointing to the existence of a brain virome where certain viruses co-occur. We further hypothesize that distinct virome profiles are linked to different forms of NDs.

Thrombus causes fluctuations in arterial drug delivery from intravascular stents.

Arterial drug concentrations determine local toxicity. As such the emergent safety concerns surrounding drug-eluting stents mandate an investigation of the factors contributing to fluctuations in arterial drug uptake. Drug-eluting stents were implanted into porcine coronary arteries, arterial drug uptake was followed and modeled using 2-dimensional computational drug transport. Arterial drug uptake in vivo occurred faster than predicted by free drug diffusion, thus an alternate, mechanism for rapid transport has been proposed involving carrier-mediated transport. Though there was minimal variation in vivo in release kinetics from stent to stent, arterial drug deposition varied by up to 114% two weeks after stent implantation. The extent of adherent mural thrombus also fluctuated by 113% within 3 days after implantation. The computational drug transport model predicted that focal and diffuse thrombi elevate arterial drug deposition in proportion to the thrombus size by reducing drug washout subsequently increasing local drug availability. Fluctuations in arterial drug uptake are commonly reported. We now explain that variable peristrut thrombus can explain such observations even in the face of a narrow range of drug release from the stent. The mural thrombus effects on arterial drug deposition may be circumvented by forcing slow, rate limiting arterial transport that cannot be further hindered by mural thrombus.

Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution.

Millions of patients worldwide have received drug-eluting stents to reduce their risk for in-stent restenosis. The efficacy and toxicity of these local therapeutics depend upon arterial drug deposition, distribution, and retention. To examine how administered dose and drug release kinetics control arterial drug uptake, a model was created using principles of computational fluid dynamics and transient drug diffusion-convection. The modeling predictions for drug elution were validated using empiric data from stented porcine coronary arteries. Inefficient, minimal arterial drug deposition was predicted when a bolus of drug was released and depleted within seconds. Month-long stent-based drug release efficiently delivered nearly continuous drug levels, but the slow rate of drug presentation limited arterial drug uptake. Uptake was only maximized when the rates of drug release and absorption matched, which occurred for hour-long drug release. Of the two possible means for increasing the amount of drug on the stent, modulation of drug concentration potently impacts the magnitude of arterial drug deposition, while changes in coating drug mass affect duration of release. We demonstrate the importance of drug release kinetics and administered drug dose in governing arterial drug uptake and suggest novel drug delivery strategies for controlling spatio-temporal arterial drug distribution.

Strut position, blood flow, and drug deposition: implications for single and overlapping drug-eluting stents.

BACKGROUND: The intricacies of stent design, local pharmacology, tissue biology, and rheology preclude an intuitive understanding of drug distribution and deposition from drug-eluting stents (DES). METHODS AND RESULTS: A coupled computational fluid dynamics and mass transfer model was applied to predict drug deposition for single and overlapping DES. Drug deposition appeared not only beneath regions of arterial contact with the strut but surprisingly also beneath standing drug pools created by strut disruption of flow. These regions correlated with areas of drug-induced fibrin deposition surrounding DES struts in porcine coronary arteries. Fibrin deposition immediately distal to individual isolated drug-eluting struts was twice as great as in the proximal area and for the stent as a whole was greater in distal segments than proximal segments. Adjacent and overlapping stent struts increased computed arterial drug deposition by far less than the sum of their combined drug load. In addition, drug eluted from the abluminal stent strut surface accounted for only 11% of total deposition, whereas, remarkably, drug eluted from the adluminal surface accounted for 43% of total deposition. Thus, local blood flow alterations and location of drug elution on the strut were far more important in determining arterial wall drug deposition and distribution than were drug load or arterial wall contact with coated strut surfaces. CONCLUSIONS: Simulations that coupled strut configurations with flow dynamics correlated with in vivo effects and revealed that drug deposition occurs less via contact between drug coating and the arterial wall than via flow-mediated deposition of blood-solubilized drug.