Current therapeutic strategies and possible effective drug delivery strategies against COVID-19.

COVID-19 pandemic is the biggest global crisis. The frequent mutations in coronavirus to generate new mutants is of major concern. The pathophysiology of SARS-CoV-2 infection has been well studied to find out suitable molecular targets and candidate drugs for effective treatment. FDA-recommended etiotropic therapies are currently followed along with mass vaccination. The drug delivery system and the route of administration have a great role to enhance the efficacy of therapeutic agents and vaccines. Since COVID-19 primarily infects the lungs in the affected individuals, pulmonary administration may be the best possible route for the treatment of COVID-19. Liposomes, solid lipid nanoparticles, polymeric nanoparticles, porous microsphere, dendrimers, and nanoparticles encapsulated microparticles are the most suitable drug delivery systems for targeted drug delivery. The solubility, permeability, chemical stability, and biodegradability of drug molecules are the key factors for the right selection of suitable nanocarriers. The application of nanotechnology has been instrumental in the successful development of mRNA, DNA and subunit vaccines, as well as the delivery of COVID-19 therapeutic agents.

Current therapeutic delivery approaches using nanocarriers for the treatment of tuberculosis disease.

Tuberculosis is a major health issue globally and a leading cause of death due to the infective microorganism Mycobacterium tuberculosis. Treatment of drug resistance tuberculosis requires longer treatment with multiple daily doses of drugs. Unfortunately, these drugs are often associated with poor patient compliance. In this situation, a need has been felt for the less toxic, shorter, and more effective treatment of the infected tuberculosis patients. Current research to develop novel anti-tubercular drugs shows hope for better management of the disease. Research on drug targeting and precise delivery of the old anti-tubercular drugs with the help of nanotechnology is promising for effective treatment. This review has discussed the status currently available treatments for tuberculosis patients infected with Mycobacterium alone or in comorbid conditions like diabetes, HIV and cancer. This review also highlighted the challenges in the current treatment and research on the novel anti-tubercular drugs to prevent multi-drug-resistant tuberculosis. It presents the research highlights on the targeted delivery of anti-tubercular drugs using different nanocarriers for preventing multi-drug resistant tuberculosis. Report has shown the importance and development of the research on nanocarriers mediated anti-tubercular delivery of the drugs to overcome the current challenges in tuberculosis treatment.

Coating of favipiravir (FVP) on silver nanoparticles: First principle study

Silver nanoparticles, thanks to their antiviral and antibacterial properties, have great potential in a variety of applications, such as drug-delivery carriers. The coating properties of silver nanoparticles (size range of 1.6 nm) with a well-known drug, Favipirair, were investigated in this study using quantum mechanical and classical atomistic molecular dynamics simulation in order to use as the drug delivery to treat COVID-19 disease. The drug molecule's optimized structure, frequencies, charge distribution, and electrostatic potential maps were simulated using density functional theory (DFT) at the B3LYP/6–311++g(d,p) level of theory. The coating of AgNP with each of these drugs was then studied using molecular dynamics simulation. The interaction affinity obtained from MD results agrees with the DFT results on drug adsorption on the Ag(1 1 1) slab. © 2023

Covalent organic frameworks and metal-organic frameworks against pathogenic viruses and antibiotic-resistant bacteria: Diagnostic and therapeutic applications

Antimicrobial resistance and antiviral infections statistics show that the number of global cases has been exponentially increasing;thus there is an unmet need for developing alternatives rather than to continue conventional strategies such as antibiotic administration, since they failed to show promise especially during the past few decades. Among different porous materials, metal-organic frameworks (MOFs) are a class of porous coordination polymers broadly explored in nano- and biomedicine due to their desirable properties, including excellent surface area, structural variability, the richness of their crystal structures/architectures, allowing for engineering synergies between metal nodes, functional linkers, encapsulated substrates or nanoparticles, heterogeneous catalysis, ion exchange, controlled and targeted drug delivery, energetics, etc. MOF-based sensing platforms have shown suitable potentials for specific viral detection. Covalent organic frameworks (COFs) are porous crystalline organic materials with two- or three-dimensional structures, which can be employed for reducing the interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) in addition to other inhibitory effects. These frameworks can be applied for encapsulating antibiotics or antiviral agents against pathogens;they have been also studied for photodynamic inactivation of pathogenic bacteria. Herein, the most recent advancements pertaining to the applications of these frameworks for specific detection and inhibition of pathogenic viruses and antibiotic-resistant bacteria are cogitated, focusing on important challenges and perspectives. This review also provides expert recommendations on the future development and utility of these frameworks to manage antimicrobial resistance and infectious diseases more efficiently. © 2023 Elsevier Ltd

A comparative DFT study on Al- and Si- doped single-wall carbon nanotubes (SWCNTs) for Ribavirin drug sensing and detection

In this work, we have presented a comparative study on Ribavirin (RBV) drug sensing and detection on the pristine and functionalized single-wall carbon nanotubes (f-SWCNTs) by Density Functional Theory (DFT) method. The pristine and metal-doped zigzag (4,0) and (6,0) SWCNTs were first considered for the RBV adsorption. All the probable positions of RBV adsorption were investigated to find which one is energetically favourable. The topology analysis of the Quantum theory of atoms in a molecule (QTAIM) with non-covalent interactions (NCI-RDG), Frontier molecular orbitals (FMO), Density of states (DOS), and non-linear optical (NLO) analysis were carried out to understand the molecular structure, electrical, electronic and optical properties of complexes. The charge analysis indicates that charge transfer is from the adsorbed RBV to the pristine and metal-doped (4,0) and (6,0) SWCNTs. The highest values of adsorption energies for Al-, Si-doped and pristine (4,0) SWCNTs were determined as −34.688, −87.999 and −10.382 kcal/mol, respectively, whereas corresponding values for metal-doped and pristine (6,0) SWCNTs are about −43.592, −20.661 and −12.414 kcal/mol, respectively. The results suggest that those bare and metal-doped (4,0) SWCNTs and (6,0) Si-SWCNTs can serve as promising sensors in practical applications to detect, recognize and carrier RBV drug for its medicinal drug delivery applications. Based on the NLO properties of (6,0) Si-SWCNTs and pristine (6,0) SWCNT (with an acceptable recovery time of 279s and first hyper polarizability value of β = 229.25 × 10−30 cm5 esu−1), those nanotubes may be possible candidates to be used as the optoelectronic sensor for RBV drug. The appropriate short length of nanotubes was obtained. © Elsevier Ltd

Viruses as biomaterials

Viruses lacking the capacity to infect mammals exhibit minimal toxicity, good biocompatibility, and well-defined structures. As self-organized biomolecular assemblies, they can be produced from standard biological techniques on a large scale at a low cost. Genetic, chemical, self-assembly, and mineralization techniques have been applied to allow them to display functional peptides or proteins, encapsulate therapeutic drugs and genes, assemble with other materials, and be conjugated with bioactive molecules, enabling them to bear different biochemical properties. So far, a variety of viruses (infecting bacteria, plants, or animals), as well as their particle variants, have been used as biomaterials to advance human disease prevention, diagnosis, and treatment. Specifically, the virus-based biomaterials can serve as multifunctional nanocarriers for targeted therapy, antimicrobial agents for infectious disease treatment, hierarchically structured scaffolds for guiding cellular differentiation and promoting tissue regeneration, versatile platforms for ultrasensitive disease detection, tissue-targeting probes for precision bioimaging, and effective vaccines and immunotherapeutic agents for tackling challenging diseases. This review provides an in-depth discussion of these exciting applications. It also gives an overview of the viruses from materials science perspectives and attempts to correlate the structures, properties, processing, and performance of virus-based biomaterials. It describes the use of virus-based biomaterials for preventing and treating COVID-19 and discusses the challenges and future directions of virus-based biomaterials research. It summarizes the progressive clinical trials of using viruses in humans. With the impressive progress made in the exciting field of virus-based biomaterials, it is clear that viruses are playing key roles in advancing important areas in biomedicine such as early detection and prevention, drug delivery, infectious disease treatment, cancer therapy, nanomedicine, and regenerative medicine. © 2023 Elsevier B.V.

New insights from nanotechnology in SARS-CoV-2 detection, treatment strategy, and prevention.

The recent outbreak of SARS-CoV-2 resulted into the deadly COVID-19 pandemic, which has made a profound impact on mankind and the world health care system. SARS-CoV-2 is mainly transmitted within the population via symptomatic carriers, enters the host cell via ACE2 and TMPSSR2 receptors and damages the organs. The standard diagnostic tests and treatment methods implemented lack required efficiency to beat SARS-CoV-2 in the race of its spreading. The most prominently used diagnostic test,reverse transcription-polymerase chain reaction (a nucleic acid-based method), has limitations including a prolonged time taken to reveal results, limited sensitivity, a high rate of false negative results, and lacking specificity due to a homology with other viruses. Furthermore, as part of the treatment, antiviral drugs such as remdesivir, favipiravir, lopinavir/ritonavir, chloroquine, daclatasvir, atazanavir, and many more have been tested clinically to check their potency for the treatment of SARS-CoV-2 but none of these antiviral drugs are the definitive cure or suitable prophylaxis. Thus, it is always required to combat SARS-CoV-2 spread and infection for a better and precise prognosis. This review answers the above mentioned challenges by employing nanomedicine for the development of improved detection, treatment, and prevention strategies for SARS-CoV-2. In this review, nanotechnology-based detection methods such as colorimetric assays, photothermal biosensors, molecularly imprinted nanoparticles sensors, electrochemical nanoimmunosensors, aptamer-based biosensors have been discussed. Furthermore, nanotechnology-based treatment strategies involving polymeric nanoparticles, metallic nanoparticles, lipid nanoparticles, and nanocarrier-based antiviral siRNA delivery have been depicted. Moreover, SARS-CoV-2 prevention strategies, which include the nanotechnology for upgrading personal protective equipment, facemasks, ocular protection gears, and nanopolymer-based disinfectants, have been also reviewed. This review will provide a one-site informative platform for researchers to explore the crucial role of nanomedicine in managing the COVID-19 curse more effectively.

Inhalation of L-arginine-modified liposomes targeting M1 macrophages to enhance curcumin therapeutic efficacy in ALI.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), characterized by uncontrolled lung inflammation, is one of the most devastating diseases with high morbidity and mortality. As the first line of defense system, macrophages play a crucial role in the pathogenesis of ALI/ARDS. Therefore, it has great potential to selectively target M1 macrophages to improve the therapeutic effect of anti-inflammatory drugs. L-arginine plays a key role in regulating the immune function of macrophages. The receptors mediating L-arginine uptake are highly expressed on the surface of M1-type macrophages. In this study, we designed an L-arginine-modified liposome for aerosol inhalation to target M1 macrophages in the lung, and the anti-inflammatory drug curcumin was encapsulated in liposomes as model drug. Compared with unmodified curcumin liposome (Cur-Lip), L-arginine functionalized Cur-Lip (Arg-Cur-Lip) exhibited higher uptake by M1 macrophages in vitro and higher accumulation in inflamed lungs in vivo. Furthermore, Arg-Cur-Lip showed more potent therapeutic effects in LPS-induced RAW 264.7 cells and the rat model of ALI. Overall, these findings indicate that L-arginine-modified liposomes have great potential to enhance curcumin treatment of ALI/ARDS by targeting M1 macrophages, which may provide an option for the treatment of acute lung inflammatory diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome and middle east respiratory syndrome.

Engineered self-healing single-cavity microcapsules for pulsatile release of drug delivery

A wide range of polymer-based drug delivery systems have been reported for the treatment of various diseases. However, the dosing regimen of many drugs, such as stimulator of interferon genes agonists, programmed cell death protein-1 antibodies, and coronavirus disease 2019 vaccines, consists of repeated intratumoral or intramuscular injections. These repeated administrations may lead to poor adherence, thus resulting in compromised therapeutic outcomes and increased financial burden. Here, we developed a multidose drug delivery platform by engineering polylactic-co-glycolic acid (PLGA) with different molecular weights into self-healing single-cavity microcapsules (SSM). This approach showed a flexible collocation strategy to achieve customized pulsatile drug release and was fully degradable with good safety. Notably, this single-injection delivery system contains only PLGA, holding great promise for clinical translation. © 2022 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences

Water-soluble inclusion complexes for a novel anti-viral agent with low toxicity;Oseltamivir with the β-cyclodextrins

An innovative sonication method has been developed to produce inclusion complexes (ICs) of Oseltamivir (OTV) which is a potentially water-soluble anti-viral agent with lesser cytotoxicity. Proton signals and chemical shifts of OTV without any ambiguity confirm the formation of ICs with β-Cyclodextrin (B-CD) and Hydroxypropyl-β-cyclodextrin (H-CD). ICs are also supported by their atomic percentages as secondary evidence using XPS analysis. Analysis of drug release at three pH levels revealed the slow release of the OTV from ICs and also suitable for viral inactivation. A very less cytotoxic ability on cancer cell lines and enhanced the viral inactivation of OTV after being made into water-soluble ICs. © 2022 Elsevier B.V.

Plant Exosomal Vesicles: Perspective Information Nanocarriers in Biomedicine

Exosomal nanoparticles (exosomes or nanovesicles) are biogenic membrane vesicles secreted by various cell types and represent a conservative mechanism of intercellular and interspecies communication in pro- and eukaryotic organisms. By transporting specific proteins, nucleic acids, and low molecular weight metabolites, the exosomes are involved in the regulation of developmental processes, activation of the immune system, and the development of a protective response to stress. Recently, the plant nanovesicles, due to an economical and affordable source of their production, have attracted a lot of attention in the biomedical field. Being a natural transport system, the plant exosomes represent a promising platform in biomedicine for the delivery of molecules of both endogenous and exogenous origin. This review presents current data on the biogenesis of plant exosomes and their composition, as well as mechanisms of their loading with various therapeutic compounds, which are determining factors for their possible practical use. We believe that further research in this area will significantly expand the potential of targeted therapy, particularly targeted gene regulation via the small RNAs, due to the use of plant exosomes in clinical practice.

Intelligent Drug Delivery Vehicle System Based on STM32

In the context of the new coronavirus epidemic, medical systems throughout the world has suffered tremendous pressure, the most intuitive problem is a shortage of human resources. In this regard, the 'intelligent drug delivery vehicle' puts forward a feasible scheme, which can replace manual work in a specific hospital area to complete the delivery of drugs. The system is based on STM32F103ZET6 core processor, controlling the OpenMV visual module to identify the hospital corridor information, and then through the pressure detection module, gray detection tracking module and angle sensing module information, the core processor controls the motor drive module to make the vehicle move. The system modifies the algorithm under the traditional NCC template matching algorithm, and uses the zoom image to reduce the pixels which improve the camera frame rate and recognition accuracy. At the same time, the Bluetooth communication module is installed to enable different vehicles to execute the drug delivery operations at the same time, therefore reducing manual work saving. © 2022 IEEE.

IoT Enabled Therapeutical Assistance Unit for COPD Patient Drug Delivery and Management

Chronic Obstructive Pulmonary Disease (COPD) results in progressive airflow limitation caused by an inflammatory reaction in the lungs due to the inhalation of noxious particles of gas, and this is the third dominant cause of death globally. Proper management and care can reduce risk factors and complications to improve the quality of life. In the covid situation due to the sudden increase in workload for doctors and Nurses, the regular COPD patients of the hospital were to face problems in proper drug administration and monitoring during infusion and nebulization and, also proper continuous monitoring of some critical parameters like SPO2, ECG, etc. This proper monitoring and controlling of critical cases by the physician at a distinct place away from the patient by smartphone is very much essential. To fulfill these requirements the proposed system involves the integration of medical devices that supports two different drug delivery system with an oxygen facility and continuous monitoring of vital parameters. This is real-time implantation using Atmega328 IC and IOT to overcome the technical shortcoming and to enhance the safety of COPD patients. In one section IR sensor with IR LED and the photodiode is used for monitoring drop rate count and volume infused during infusion. In the other section, the Arduino Nano microcontroller directs the MOSFET to control the speed and time during Nebulization. Here, the On and Off of the system can be done both manually and digitally. Blynk application is used to read and visualize sensor data and to control the hardware remotely. This system saves resources and time simultaneously and aids to improves the patient's quality of life. © 2022 IEEE.

Targeted delivery of inhalable drug particles in a patient-specific tracheobronchial tree with moderate COVID-19: A numerical study.

The coronavirus disease 2019 (COVID-19) pandemic has led to severe social and economic disruption worldwide. Although currently no consent has been reached on a specific therapy that can treat COVID-19 effectively, several inhalation therapy strategies have been proposed to inhibit SARS-CoV-2 infection. These strategies include inhalations of antiviral drugs, anti-inflammatory drugs, and vaccines. To investigate how to enhance the therapeutic effect by increasing the delivery efficiency (DE) of the inhaled aerosolized drug particles, a patient-specific tracheobronchial (TB) tree from the trachea up to generation 6 (G6) with moderate COVID-19 symptoms was selected as a testbed for the in silico trials of targeted drug delivery to the lung regions with pneumonia alba, i.e., the severely affected lung segments (SALS). The 3D TB tree geometry was reconstructed from spiral computed tomography (CT) scanned images. The airflow field and particle trajectories were solved using a computational fluid dynamics (CFD) based Euler-Lagrange model at an inhalation flow rate of 15 L/min. Particle release maps, which record the deposition locations of the released particles, were obtained at the inlet according to the particle trajectories. Simulation results show that particles with different diameters have similar release maps for targeted delivery to SALS. Point-source aerosol release (PSAR) method can significantly enhance the DE into the SALS. A C++ program has been developed to optimize the location of the PSAR tube. The optimized simulations indicate that the PSAR approach can at least increase the DE of the SALS by a factor of 3.2× higher than conventional random-release drug-aerosol inhalation. The presence of the PSAR tube only leads to a 7.12% change in DE of the SALS. This enables the fast design of a patient-specific treatment for reginal lung diseases.

Design of AGV Structure and Control System for Hospital Drug Delivery

Because of the outbreak of COVID-19, “contactless distribution” will become the main direction of future medical logistics and transportation. In order to realize the distribution mode, the hospital drug delivery AGV is designed, including structure design and control system design. The structure design adopts induction line pilotage, wheel structure of three row-six wheel and double-wheel differential driving structure, and uses 3D software for structure modeling. The design of the control system adopts fuzzy control to adjust AGV wheel speed to realize the automatic deviation correction function when AGV is running, and the simulation of the automatic deviation correction control system is carried out. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Autonomous Bot Assistant in Covid-19 Patient Isolation Wards

Objective: In the current coronavirus situation around the globe, there are many challenges in front of the doctors health workers carrying out their duty in hospitals/isolation wards. The direct contact with affected patients despite ensuring safety measures has led to the loss of many lives of the frontline workers. Thus, it is valuable to design an autonomous robot system that can fulfill daily chores in the isolation ward. Method: In this paper, we design a robotic system to fulfill the daily requirements of a patient such as delivering meals medicines, also it can collect health stats such as SPO2 body temperature. The robot traces a line that leads it to the beds in the isolation ward, an RFID tag reader is installed on the robot that detects the RFID cards placed on the bed. Then the robot conveys the patients through the display to place a finger on the SPO2 sensor temperature sensor, this recorded data is instantly stored through ESP8266 on a ThingSpeak server in the patient's database. Results: The robot can achieve its objective, with exact blood oxygen saturation readings approximate body temperature reading. The daily meals medicines are delivered in a package having a label of bed number on it. Conclusions: This study contributes the first cost-effective robot with a combination of unique features in a total project cost of INR 7000(approx.95USD). The routine work of health workers is replaced alternatively by an autonomous robot, thus preventing direct contact with patients. © 2021 IEEE.

Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.

Injuries to the central nervous system (CNS) such as stroke, brain, and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration. The brain has a surprising intrinsic capability of recovering itself after injury. However, the hostile extrinsic microenvironment significantly hinders axon regeneration. Recent advances have indicated that the inactivation of intrinsic regenerative pathways plays a pivotal role in the failure of most adult CNS neuronal regeneration. Particularly, substantial evidence has convincingly demonstrated that the mechanistic target of rapamycin (mTOR) signaling is one of the most crucial intrinsic regenerative pathways that drive axonal regeneration and sprouting in various CNS injuries. In this review, we will discuss the recent findings and highlight the critical roles of mTOR pathway in axon regeneration in different types of CNS injury. Importantly, we will demonstrate that the reactivation of this regenerative pathway can be achieved by blocking the key mTOR signaling components such as phosphatase and tensin homolog (PTEN). Given that multiple mTOR signaling components are endogenous inhibitory factors of this pathway, we will discuss the promising potential of RNA-based therapeutics which are particularly suitable for this purpose, and the fact that they have attracted substantial attention recently after the success of coronavirus disease 2019 vaccination. To specifically tackle the blood-brain barrier issue, we will review the current technology to deliver these RNA therapeutics into the brain with a focus on nanoparticle technology. We will propose the clinical application of these RNA-mediated therapies in combination with the brain-targeted drug delivery approach against mTOR signaling components as an effective and feasible therapeutic strategy aiming to enhance axonal regeneration for functional recovery after CNS injury.

Targeting vascular inflammation through emerging methods and drug carriers.

Acute inflammation is a common dangerous component of pathogenesis of many prevalent conditions with high morbidity and mortality including sepsis, thrombosis, acute respiratory distress syndrome (ARDS), COVID-19, myocardial and cerebral ischemia-reperfusion, infection, and trauma. Inflammatory changes of the vasculature and blood mediate the course and outcome of the pathology in the tissue site of insult, remote organs and systemically. Endothelial cells lining the luminal surface of the vasculature play the key regulatory functions in the body, distinct under normal vs. pathological conditions. In theory, pharmacological interventions in the endothelial cells might enable therapeutic correction of the overzealous damaging pro-inflammatory and pro-thrombotic changes in the vasculature. However, current agents and drug delivery systems (DDS) have inadequate pharmacokinetics and lack the spatiotemporal precision of vascular delivery in the context of acute inflammation. To attain this level of precision, many groups design DDS targeted to specific endothelial surface determinants. These DDS are able to provide specificity for desired tissues, organs, cells, and sub-cellular compartments needed for a particular intervention. We provide a brief overview of endothelial determinants, design of DDS targeted to these molecules, their performance in experimental models with focus on animal studies and appraisal of emerging new approaches. Particular attention is paid to challenges and perspectives of targeted therapeutics and nanomedicine for advanced management of acute inflammation.

2AI&7D Model of Resistomics to Counter the Accelerating Antibiotic Resistance and the Medical Climate Crisis

The antimicrobial resistance (AMR) crisis is referred to as ‘Medical Climate Crisis’. Inappropriate use of antimicrobial drugs is driving the resistance evolution in pathogenic microorganisms. In 2014 it was estimated that by 2050 more people will die due to antimicrobial resistance compared to cancer. It will cause a reduction of 2% to 3.5% in Gross Domestic Product (GDP) and cost the world up to 100 trillion USD. The indiscriminate use of antibiotics for COVID-19 patients has accelerated the resistance rate. COVID-19 reduced the window of opportunity for the fight against AMR. This man-made crisis can only be averted through accurate actionable antibiotic knowledge, usage, and a knowledge driven Resistomics. In this paper, we present the 2AI (Artificial Intelligence and Augmented Intelligence) and 7D (right Diagnosis, right Disease-causing-agent, right Drug, right Dose, right Duration, right Documentation, and De-escalation) model of antibiotic stewardship. The resistance related integrated knowledge of resistomics is stored as a knowledge graph in a Neo4j properties graph database for 24 × 7 access. This actionable knowledge is made available through smartphones and the Web as a Progressive Web Applications (PWA). The 2AI&7D Model delivers the right knowledge at the right time to the specialists and non-specialist alike at the point-of-action (Stewardship committee, Smart Clinic, and Smart Hospital) and then delivers the actionable accurate knowledge to the healthcare provider at the point-of-care in realtime. © 2021, Springer Nature Switzerland AG.