Niclosamide (NIC), a conventional anthelmintic agent, is emerging as a repurposed drug for COVID-19 treatment. However, the clinical efficacy is very limited due to its low oral bioavailability resulting from its poor aqueous solubility. In the present study, a new hybrid drug delivery system made of NIC, montmorillonite (MMT), and Tween 60 is proposed to overcome this obstacle. At first, NIC molecules were immobilized into the interlayer space of cationic clay, MMT, to form NIC–MMT hybrids, which could enhance the solubility of NIC, and then the polymer surfactant, Tween 60, was further coated on the external surface of NIC–MMT to improve the release rate and the solubility of NIC and eventually the bioavailability under gastrointestinal condition when orally administered. Finally, we have performed an in vivo pharmacokinetic study to compare the oral bioavailability of NIC for the Tween 60-coated NIC–MMT hybrid with Yomesan®, which is a commercially available NIC. Exceptionally, the Tween 60-coated NIC–MMT hybrid showed higher systemic exposure of NIC than Yomesan®. Therefore, the present NIC–MMT–Tween 60 hybrid can be a potent NIC drug formulation with enhanced solubility and bioavailability in vivo for treating Covid-19.
COVID-19 has been affecting millions of individuals worldwide and, thus far, there is no accurate therapeutic strategy. This critical situation necessitates novel formulations for already existing, FDA approved, but poorly absorbable drug candidates, such as niclosamide (NIC), which is of great relevance. In this context, we have rationally designed NIC-loaded hydrotalcite composite nanohybrids, which were further coated with Tween 60 or hydroxypropyl methyl cellulose (HPMC), and characterized them in vitro. The optimized nanohybrids showed particle sizes <300 nm and were orally administrated to rats to determine whether they could retain an optimum plasma therapeutic concentration of NIC that would be effective for treating COVID-19. The pharmacokinetic (PK) results clearly indicated that hydrotalcite-based NIC formulations could be highly potential options for treating the ongoing pandemic and we are on our way to understanding the in vivo anti-viral efficacy sooner. It is worth mentioning that hydrotalcite–NIC nanohybrids maintained a therapeutic NIC level, even above the required IC50 value, after just a single administration in 8–12 h. In conclusion, we were very successfully able to develop a NIC oral formulation by immobilizing with hydrotalcite nanoparticles, which were further coated with Tween 60 or HPMC, in order to enhance their emulsification in the gastrointestinal tract.
This paper presents an integrated control algorithm for a compound hybrid excavator. Both conventional hydraulic excavator and compound hybrid excavator models are developed to compute fuel consumption. The excavator simulation models, which consist of engine, pump and electric components have been validated with test data. To design the hybrid system's integrated control algorithm which determines the output power of two motor/generators and ultra capacitor, a rule-based control algorithm to improve fuel economy is proposed. Simulation studies have been conducted for a typical digging process to investigate the performance of the proposed rulebased controller. Simulation results show that 26% reduction of fuel consumption can be obtained using the proposed controller to the compound hybrid excavator compared to the conventional hydraulic excavator.
In recent years, container-based virtualization technology for edge and cloud computing has advanced dramatically. Virtualization solutions based on Docker Containers provide a more lightweight and efficient virtual environment for Edge and cloud-based applications. Because their use is growing on its own and is still in its early phases, these technologies will face a slew of security issues. Vulnerabilities and malware in Docker container images are two serious security concerns. The risk of privilege escalation is increased because Docker containers share the Linux kernel. This study presents a distributed system framework called Safe Docker Image Sharing with Homomorphic Encryption and Blockchain (SeDIS-HEB). Through homomorphic encryption, authentication, and access management, SeDIS-HEB provides secure docker image sharing. The SeDIS-HEB framework prioritizes the following three major functions: (1) secure docker image upload, (2) secure docker image sharing, and (3) secure docker image download. The proposed framework was evaluated using the InterPlanetary File System (IPFS). Secure Docker images were uploaded using IPFS, preventing unauthorized users from accessing the data contained within the secure Docker images. The SeDIS-HEB results were transparent and ensured the quality of blockchain data access control authentication, docker image metadata denial-of-service protection, and docker image availability.
Although nicotinic acid (NA) has several clinical benefits, its potency cannot be fully utilized due to several undesirable side effects, including cutaneous flushing, GIT-associated symptoms, etc. To overcome such issues and improve the NA efficacy, a new inorganic–organic nanohybrids system was rationally designed. For making such a hybrid system, NA was intercalated into LDH through a coprecipitation technique and then coated with Eudragit® S100 to make the final drug delivery system called Eudragit® S100-coated NA-LDH. The as-made drug delivery system not only improved the NA release profile but also exhibited good bio-compatibility as tested on L929 cells. Such an inorganic–organic nanohybrid drug delivery agent is expected to reduce the undesirable side effects associated with NA and hopefully improve the pharmacological effects without inducing any undesirable toxicity.
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