ABSTRACT
COVID-19 is a highly contagious coronavirus that has caused traumatic global havoc. By September 14, 2021, there were 224+ million confirmed cases and 4.6+ million fatalities world-wide [1]. Internet of Things (IoT)-based quarantine strategies effectively slow down and prevent COVID-19 transmission [2]. However, the unstan-dardized quarantine strategy may cause negative consequences. Typically, quarantine deactivates normal economic interactions, thus causing huge economic loss [3]. Moreover, the lack of versatility and resiliency also brings safety challenges on some occasions. In this investigation, a performance scoring quarantine index, referred to as QDex, is developed to provide guidance for a new concept of dynamic geofencing quarantine directive. QDex evaluation features adaptive dynamic geofencing (QEDG) for quarantine. In QEDG, QDex is newly defined to evaluate the dynamic geofencing in relation to epidemic control and economic loss. They are represented by two formulated indicators, namely the transmission risk (TR) and the active profit (AP), which are related to the isolator bio status (e.g., body temperature). Based on the evaluation results of TR and AP, QEDG provides a proper geofencing indication for quarantine, which decreases epidemic transmission and restores economic recovery. The requirement-based applicable communication technologies for QEDG are discussed and analyzed, and two typical use cases are included. Finally, the limitations and challenges of QEDG are discussed.
ABSTRACT
The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.
Subject(s)
Drug Carriers/chemistry , Lung/metabolism , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Lung/drug effects , Lung Diseases/drug therapy , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Peptides/therapeutic use , Proteins/therapeutic useABSTRACT
The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic as declared by World Health Organization (WHO). In the absence of an effective treatment, different drugs with unknown effectiveness, including antimalarial hydroxychloroquine (HCQ), with or without concurrent administration with azithromycin (AZM), have been tested for treating COVID-19 patients with developed pneumonia. However, the efficacy and safety of HCQ and/or AZM have been questioned by recent clinical reports. Direct effects of these drugs on the human heart remain very poorly defined. To better understand the mechanisms of action of HCQ +/- AZM, we employed bioengineered human ventricular cardiac tissue strip (hvCTS) and anisotropic sheet (hvCAS) assays, made with human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCMs), which have been designed for measuring cardiac contractility and electrophysiology, respectively. Our hvCTS experiments showed that AZM induced a dose-dependent negative inotropic effect which could be aggravated by HCQ; electrophysiologically, as revealed by the hvCAS platform, AZM prolonged action potentials and induced spiral wave formations. Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.