ABSTRACT
The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to mediate intercellular communications. The exosomal cargo serves as biomarkers in diagnosing various diseases; moreover, exosomes could be employed as nanocarriers in drug delivery systems. Exosomes look promising to combat the current pandemic since they contribute to the immune response against several viral pathogens. Many studies have proved the potential of using exosomes either as viral elements or host systems that acquire immune-stimulatory effects and could be used as a vaccine or drug delivery tool. It is essential to stop viral replication, prevent and reverse the massive storm of cytokine that worsens the infected patients' situations for the management of COVID-19. The main benefits of exosomes could be; no cells will be introduced, no chance of mutation, lack of immunogenicity and the damaged genetic material that could negatively affect the recipient is avoided. Additionally, it was found that exosomes are static with no ability for in vivo reproduction. The current review article discusses the possibilities of using exosomes for detecting novel coronavirus and summarizes state of the art concerning the clinical trials initiated for examining the use of COVID-19 specific T cells derived exosomes and mesenchymal stem cells derived exosomes in managing COVID-19.
ABSTRACT
Background: Asiatic acid (AA) is a naturally occurring triterpenoid derivative of Centella asiatica (CA) with neuroprotective effect. The study aimed to design an ideal oral drug delivery system to treat Alzheimer's disease (AD) and develop chitosan-embedded liposomes comprising an extract of CA (CLCAE) and compare them with the chitosan-coated liposomes of asiatic acid (CLAA) for oral delivery to treat the initial phases of AD. Methods: The solvent evaporation technique was used to develop CLCAE and CLAA, optimised with the experiment's design, and was further evaluated. Results: Nuclear magnetic resonance (NMR) studies confirmed coating with chitosan. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) indicated the successful formation of CLCAE and CLAA. Differential scanning colorimetry (DSC) confirmed the drug-phospholipid complex. Furthermore, the rate of in vitro release of CLCAE and CLAA was found to be 69.43±0.3 % and 85.3±0.3 %, respectively, in 24 h. Ex vivo permeation of CLCAE and CLAA was found to be 48±0.3 % and 78±0.3 %, respectively. In the Alcl3-induced AD model in rats, disease progression was confirmed by Y-maze, the preliminary histopathology evaluation showed significantly higher efficacy of the prepared liposomes (CLCAE and CLAA) compared to the Centella asiatica extract (CAE) and they were found to have equivalent efficacy to the standard drug (rivastigmine tartrate). The considerable increase in pharmacodynamic parameters in terms of neuronal count in the CLAA group indicated the protective role against Alcl3 toxicity and was also confirmed by assessing acetylcholine (Ach) levels. The pharmacokinetic study, such as C max, T max, and area under curve (AUC) parameters, proved an increase in AA bioavailability in the form of CLAA compared to the pure AA and CLCAE forms. Conclusion: The preclinical study suggested that CLAA was found to have better stability and an ideal oral drug delivery system to treat AD.
