Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

Abstract

Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 . Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

Design, Manufacturing, Characterization and Evaluation of Lipid Nanocapsules to Enhance the Biopharmaceutical Properties of Efavirenz

“…The optimized blend 1, from the previous Section 3. 4, was used for this purpose. This one consisted of a mixture of MCT oil, crude soy lecithin, Tween 80 and NaCl-water in a ratio of 12:3:9:76% (m/m).…”

Towards the Antiviral Agents and Nanotechnology-Enabled Approaches Against Parvovirus B19

“…Drug delivery nanosystems incorporating antiviral agents embody the advantages in prolonging blood circulation time, improving cellular selectivity and controlled release, and consequently improving antiviral effects compared to free antiviral agents ( Cojocaru et al., 2020 ; Chen et al., 2021 ). And nanosystems that encapsulate anti-B19V agents would pave the way to the nanotechnology-aided B19V treatment.…”

Lipid Nanocarriers for Anti-HIV Therapeutics: A Focus on Physicochemical Properties and Biotechnological Advances

“…The speed and extent of oral drug diffusion through the mucus layer, submucosa, and epithelial cell barriers into the blood or lymphatic circulation is referred to as permeability. Low solubility and permeability thereby show that ARV drugs are poorly absorbed in the body [ 45 ]. Even after absorption, most ARV present other significant pharmacokinetic limitations, such as a short half-life that demands recurrent dose administration in a fastidious dosage regimen, which contributes to poor patient adherence [ 2 , 44 , 45 ].…”

“…Low solubility and permeability thereby show that ARV drugs are poorly absorbed in the body [ 45 ]. Even after absorption, most ARV present other significant pharmacokinetic limitations, such as a short half-life that demands recurrent dose administration in a fastidious dosage regimen, which contributes to poor patient adherence [ 2 , 44 , 45 ]. Another pharmacokinetic issue is poor body distribution of ARV, which prevents reaching certain target tissues that serve as viral reservoirs.…”