In Silico Study to Enhance Delivery Efficiency of Charged Nanoscale Nasal Spray Aerosols to the Olfactory Region Using External Magnetic Fields

Various factors and challenges are involved in efficiently delivering drugs using nasal sprays to the olfactory region to treat central nervous system diseases. In this study, computational fluid dynamics was used to simulate nasal drug delivery to (1) examine effects on drug deposition when various external magnetic fields are applied to charged particles, (2) comprehensively study effects of multiple parameters (i.e., particle aerodynamic diameter; injection velocity magnitude, angle, and position; magnetic force strength and direction), and (3) determine how to achieve the optimal delivery efficiency to the olfactory epithelium. The Reynolds-averaged Navier–Stokes equations governed airflow, with a realistic inhalation waveform implemented at the nostrils. Particle trajectories were modeled using the one-way coupled Euler–Lagrange model. A current-carrying wire generated a magnetic field to apply force on charged particles and direct them to the olfactory region. Once drug particles reached the olfactory region, their diffusion through mucus to the epithelium was calculated analytically. Particle aerodynamic diameter, injection position, and magnetic field strength were found to be interconnected in their effects on delivery efficiency. Specific combinations of these parameters achieved over 65-fold higher drug delivery efficiency compared with uniform injections with no magnetic fields. The insight gained suggests how to integrate these factors to achieve the optimal efficiency.

System-level Early-stage Modeling and Evaluation of IVR-assisted Processor Power Delivery System

Despite being employed in numerous efforts to improve power delivery efficiency, the integrated voltage regulator (IVR) approach has yet to be evaluated rigorously and quantitatively in a full power delivery system (PDS) setting. To fulfill this need, we present a system-level modeling and design space exploration framework called Ivory for IVR-assisted power delivery systems. Using a novel modeling methodology, it can accurately estimate power delivery efficiency, static performance characteristics, and dynamic transient responses under different load variations and external voltage/frequency scaling conditions. We validate the model over a wide range of IVR topologies with silicon measurement and SPICE simulation. Finally, we present two case studies using architecture-level performance and power simulators. The first case study focuses on optimal PDS design for multi-core systems, which achieves 8.6% power efficiency improvement over conventional off-chip voltage regulator module– (VRM) based PDS. The second case study explores the design tradeoffs for IVR-assisted PDSs in CPU and GPU systems with fast per-core dynamic voltage and frequency scaling (DVFS). We find 2 μs to be the optimal DVFS timescale, which not only reaps energy benefits (12.5% improvement in CPU and 50.0% improvement in GPU) but also avoids costly IVR overheads.

Performance and Feasibility of Therapeutic Vibrating Mesh Nebulizer for Ventilation Lung Scan

This study aimed to evaluate the performance of a therapeutic vibrating mesh-type nebulizer for the pulmonary delivery of radioaerosols for lung scintigraphy in healthy subjects. Six healthy subjects (mean age of 28.7 ± 6.2 y) inhaled 2 mL of Tc-99m diethylenetriaminepentaacetic acid (DTPA) and normal saline solution (20 mCi) via the therapeutic vibrating mesh nebulizer (DK010, DELBio, Taipei, Taiwan). The nebulizer’s mass median aerodynamic diameter (MMAD) is between 2.3 μm and 5.0 μm (3.47 ± 0.37 μm) and the nebulization rate is greater than 0.2 ml/min. Scintigraphy was performed to count radioaerosols in the regions of interest to determine the total and regional lung deposition and extrathoracic airway deposition of aerosols, penetration of aerosols, and radioactivity count balance. The total lung deposition of aerosols was 21.2 ± 5.2% (% ex-valve dose), 27.4 ± 8.0% (% ex-device dose) and 13.8 ± 4.1% (% initial dose) in nebulizer. The extrathoracic airway deposition was 4.8 ± 1.1%. The radioactivity count balance was 5.4 ± 3.0%. The ratio of outer vs inner lung deposition (O/I ratio, or penetration index) was 1.89 ± 0.55. The delivery efficiency and the penetration of aerosols to the peripheral lung achieved by the DELBio DK010 vibrating mesh-type nebulizer are similar to the commercialized jet-type nebulizers dedicated for radioaerosol lung scintigraphy nebulizer. The therapeutic vibrating mesh-type nebulizer (DELBio DK010) is feasible for radionuclide lung ventilation scintigraphy.

A systematic review on the modifications of extracellular vesicles: a revolutionized tool of nano-biotechnology

Background Tailoring extracellular vesicles (EVs) can bequeath them with diverse functions and efficient performance in nano-biotechnology. Engineering and modification of EVs improves the targeted drug delivery efficiency. Here, we performed systematic review of various methods for EVs modifications. Methods PubMed, Scopus, ISI Web of Science, EMBASE, and Google Scholar were searched for available articles on EVs modifications (up to March 2021). In total, 1208 articles were identified and assessed, and then only 36 articles were found eligible and included. Results Six studies demonstrate the application of click chemistry, seven studies used co-incubation, two studies used chemical transfection, four studies implicated electroporation and sonication approach for modification of EVs. Moreover, two studies utilized microfluidics as suitable approach for loading cargo into EVs, while eight studies showed freeze–thaw method as feasible for these biological nanoparticles. Conclusion Freeze–thaw approach is found to be convenient and popular among researchers for performing modifications in EVs for the purpose of targeted drug delivery loading. Clinical-grade EVs production with good clinical practices (GCPs) is challenging in the current scenario. More studies are needed to determine the best suitable approach for cargo loading of EVs that may be exploited for research and therapeutic use. Graphical Abstract

An adaptive spot placement method on Cartesian grid for pencil beam scanning proton therapy

Pencil beam scanning (PBS) proton radiotherapy (RT) offers flexible proton spot placement near treatment targets for delivering tumoricidal radiation dose to tumor targets while sparing organs-at-risk (OAR). Currently the spot placement is mostly based on a non-adaptive sampling (NS) strategy on a Cartesian grid. However, the spot density or spacing during NS is a constant for the Cartesian grid that is independent of the geometry of tumor targets, and thus can be suboptimal in terms of plan quality (e.g., target dose conformality) and delivery efficiency (e.g., number of spots). This work develops an adaptive sampling (AS) spot placement method on the Cartesian grid that fully accounts for the geometry of tumor targets. Compared with NS, AS places (1) a relatively fine grid of spots at the boundary of tumor targets to account for the geometry of tumor targets and treatment uncertainties (setup and range uncertainty) for improving dose conformality, and (2) a relatively coarse grid of spots in the interior of tumor targets to reduce the number of spots for improving delivery efficiency and robustness to the minimum-minitor-unit (MMU) constraint. The results demonstrate that (1) AS achieved comparable plan quality with NS for regular MMU and substantially improved plan quality from NS for large MMU, using merely about 10% of spots from NS, where AS was derived from the same Cartesian grid as NS; (2) on the other hand, with similar number of spots, AS had better plan quality than NS consistently for regular and large MMU.

Thinking Quantitatively of RNA-Based Information Transfer via Extracellular Vesicles: Lessons to Learn for the Design of RNA-Loaded EVs

Extracellular vesicles (EVs) are 50–1000 nm vesicles secreted by virtually any cell type in the body. They are expected to transfer information from one cell or tissue to another in a short- or long-distance way. RNA-based transfer of information via EVs at long distances is an interesting well-worn hypothesis which is ~15 years old. We review from a quantitative point of view the different facets of this hypothesis, ranging from natural RNA loading in EVs, EV pharmacokinetic modeling, EV targeting, endosomal escape and RNA delivery efficiency. Despite the unique intracellular delivery properties endowed by EVs, we show that the transfer of RNA naturally present in EVs might be limited in a physiological context and discuss the lessons we can learn from this example to design efficient RNA-loaded engineered EVs for biotherapies. We also discuss other potential EV mediated information transfer mechanisms, among which are ligand–receptor mechanisms.

Lung-targeted Macrophage Biomimetic Nanocarriers Based on Platycodon Grandiflorum Polysaccharides for Calming Cytokine Storm in Pneumonia

Background Pneumonia is a life-threatening respiratory disease without effective treatment due to uncontrolled inflammation of the lung tissue. Suppression of cytokine storms may be one of the keys to saving the lives of patients with severe pneumonia. Given the fragile delivery efficiency of drugs in vivo, novel delivery platforms to address these issues are necessary. Results Here, we developed a biomimetic nanocarrier (MNPs) with macrophage membranes coated ROS-responsive Platycodon grandiflorum polysaccharides nanoparticles (PNPs) for targeted delivery of curcumin (MNPs@Cur) to inflamed lungs and treat inflammation by calming cytokine storms. In the study, we could clearly find that MNPs@Cur significantly attenuated inflammation and cytokine storm syndrome in acute lung injury (ALI) mice by neutralizing multiple proinfammatory cytokines. Interestingly, we found that the PNPs also had potent pulmonary targeting compared to other polysaccharide carriers, which probably means that PNPs have inherited the natural targeting ability in the medicinal guide theory of Traditional Chinese Medicine (TCM). Conclusion The results demonstrated that the developed drug delivery system may serve as an effective and safe nanoplatform for the treatment of pneumonia, as well as provide experimental scientific basis for the medicinal guide theory of TCM and its clinical application.

Green Fabrication and Release Mechanisms of pH-Sensitive Chitosan–Ibuprofen Aerogels for Controlled Transdermal Delivery of Ibuprofen

Ibuprofen is a potent non-steroidal anti-inflammatory drug due to its analgesic, antipyretic, and anti-inflammatory actions. However, its poor solubility in water makes it difficult to manufacture ibuprofen tablets, which limited the application of ibuprofen in drug delivery systems. Polymer–drug aerogels have attracted huge interest in optimizing the drug delivery efficiency and improving the physicochemical characteristics and therapeutic quality. Here, chitosan–ibuprofen aerogels with excellent swelling, high biocompatibility, and better drug delivery efficiency were synthesized by a simple method. Our study found that the chitosan–ibuprofen aerogels exhibited remarkably improved thermal stability, excellent swelling ratio, and high drug loading. As a consequence of these favorable properties, the chitosan–ibuprofen aerogels exhibited improved drug delivery efficiency and achieved drug prolonged administration. Our study highlights the great potential of polymer–drug aerogels in improving the drug delivery efficiency of transdermal drug delivery systems.

Laboratory testing of a high efficiency light redirection system

Automated daylight redirecting slat technologies are designed to divert sunlight into the living space. They have a distinct advantage in that they can be retracted and extended, and slat angles can be adjusted according to the solar geometry and sky conditions. This study aimed to explore the geometric and photometric properties of a novel high-efficiency light redirection system (LRS). The LRS prototypes were installed in the clerestory window in the south-facing window testbed office and monitored under real sun and sky conditions. Workplane illuminance, daylight delivery efficiency (DDE) and visual comfort were evaluated. A number of simulation studies were conducted to evaluate the LRS and compare the results to the laboratory tests. The study shows that the specular properties of the slats provided significantly higher work plane illuminance and DDE. All systems showed an acceptable discomfort glare, or daylight glare probability (DGP) lower than 0.35. The comparison of the laboratory test and computer simulation was conducted using a Radiance tool. The results show that, for specular slats, the mkillum method with plastic material provided accurate work plane illuminance compared to the measurement. All simulated DGP shows accurate results compared to the laboratory test.