Pulmonary Delivery of Hydroxychloroquine Nanostructured Lipid Carrier as a Potential Treatment of COVID-19.
Ahmed Shaker AliMohsen Geza AlrashediOsama Abdelhakim Aly AhmedIbrahim M IbrahimPublished in: Polymers (2022)
Coronavirus Disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2. Pneumonia is considered the most severe and long-term complication of COVID-19. Among other drugs, hydroxychloroquine (HCQ) was repurposed for the management of COVID-19; however, low efficacy and cardiac toxicity of the conventional dosage form limited its use in COVID-19. Therefore, utilizing nanotechnology, a pulmonary delivery system of HCQ was investigated to overcome these limitations. HCQ was formulated in nanostructured lipid carriers (HCQ-NLCs) using the hot emulsification-ultrasonication method. Furthermore, the prepared formulation was evaluated in vitro. Moreover, the efficacy was tested in vivo in a bleomycin-induced acute lung injury mice model. Intriguingly, nanoformulations were given by the intratracheal route for 6 days. HCQ-NLCs showed a mean particle size of 277 nm and a good drug release profile. Remarkably, acute lung injury induced by bleomycin was associated with a marked elevation of inflammatory markers and histological alterations in lung tissues. Astoundingly, all these changes were significantly attenuated with HCQ-NLCs. The pulmonary delivery of HCQ-NLCs likely provided adequate targeting to lung tissues. Nevertheless, there is hope that this novel strategy will eventually lead to the improved effectiveness and diminished probability of alarming adverse drug reactions.
Keyphrases
- coronavirus disease
- respiratory syndrome coronavirus
- sars cov
- pulmonary hypertension
- adverse drug
- drug release
- randomized controlled trial
- gene expression
- lipopolysaccharide induced
- drug delivery
- systematic review
- emergency department
- type diabetes
- photodynamic therapy
- oxidative stress
- heart failure
- early onset
- endothelial cells
- mass spectrometry
- fatty acid
- high glucose
- electronic health record
- insulin resistance
- atrial fibrillation
- high fat diet induced
- respiratory failure