RBC-hitchhiking chitosan nanoparticles loading methylprednisolone for lung-targeting delivery

• Published in: Journal of controlled release Vol. 341; pp. 702 - 715
• Main Authors: Ding, Yaning, Lv, Bai, Zheng, Jinpeng, Lu, Caihong, Liu, Jingzhou, Lei, Yaran, Yang, Meiyan, Wang, Yuli, Li, Zhiping, Yang, Yang, Gong, Wei, Han, Jing, Gao, Chunsheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2022
• Subjects: Acute lung injury; Animals; Chitosan; Chitosan nanoparticle; COVID-19; Cytokine storm syndrome; Erythrocytes; Humans; Lung; Methylprednisolone; Methylprednisolone sodium succinate; Nanoparticles; Pharmaceutical Preparations; Rats; RBC-hitchhiking; SARS-CoV-2; Acute lung injury; Cytokine storm syndrome; RBC-hitchhiking; Methylprednisolone sodium succinate; Chitosan nanoparticle
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.12.018

Hyper-inflammation associated with cytokine storm syndrome causes high mortality in patients with COVID-19. Glucocorticoids, such as methylprednisolone sodium succinate (MPSS), effectively inhibit this inflammatory response. However, frequent and chronic administration of glucocorticoids at high doses leads to hormone dependence and serious side effects. The aim of the present study was to combine nanoparticles with erythrocytes for the targeted delivery of MPSS to the lungs. Chitosan nanoparticles loading MPSS (MPSS-CSNPs) were prepared and adsorbed on the surface of red blood cells (RBC-MPSS-CSNPs) by non-covalent interaction. In vivo pharmacokinetic study indicated that RBC-hitchhiking could significantly reduce the plasma concentration of the drug and prolong the circulation time. The mean residence time (MRT) and area under the curve (AUC) of the RBC-MPSS-CSNPs group were significantly higher than those of the MPSS-CSNPs group and the MPSS injection group. Moreover, in vivo imaging and tissue distribution indicated that RBC-hitchhiking facilitated the accumulation of nanoparticles loading fluorescein in the lung, preventing uptake of these nanoparticles by the liver. Furthermore, compared with the MPSS-CSNPs and MPSS treatment groups, treatment with RBC-MPSS-CSNPs considerably inhibited the production of inflammatory cytokines such as TNF-α and IL-6, and consequently attenuated lung injury induced by lipopolysaccharide in rats. Therefore, RBC-hitchhiking is a potentially effective strategy for the delivery of nanoparticles to the lungs for the treatment of acute lung injury and acute respiratory distress syndrome. The study involves preparation of chitosan nanoparticles using the ionotropic-gelation method, which were attached noncovalently to the erythrocytes obtained by centrifugation of the whole blood collected through the abdominal aorta of rats. RBC-hitchhiking facilitated delivery of the chitosan nanoparticles to the lungs to treat inflammation. [Display omitted] •RBC-hitchhiking chitosan NPs loading MPSS (RBC-MPSS-CSNPs) were developed.•RBC-MPSS-CSNPs could significantly reduce the plasma concentration of the drug and prolong the circulation time.•RBC-MPSS-CSNPs exhibited a satisfactory efficiency in lung delivery.•RBC-MPSS-CSNPs may be used against ALI / ARDS, including COVID-19 disease, or other infectious pulmonary inflammatory diseases.•The findings of this study, if applied clinically, will contribute to reducing the debilitating effects of COVID-19 across the globe.