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

Abstract

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.

pH-Responsive Polymer Nanomaterials for Tumor Therapy

“…Chemotherapeutic therapy, referred to as chemotherapy, is still one of the main methods of tumor treatment ( 11 – 13 ). Some chemical drugs, such as oxaliplatin, doxorubicin (DOX), and paclitaxel (PTX), are applied to kill tumor cells and shrink or destroy the tumor ( 14 – 18 ). Because drug delivery is generally given systemically, the body itself will also be affected and damaged to some extent, causing side effects, complications, and even death in some serious cases ( 19 – 22 ).…”

Dose-Effect Relationship of Chitosan and Danshen Combined Injection for Fallopian Tube Recanalization

“…Chitosan nanoparticles have loaded methylprednisolone sodium succinate to prolong the residence time and considerably inhibited the production of inflammatory cytokines, such as TNF-α and IL-6 ( Ding et al, 2022 ). Great efficacy was found in the healing of diabetic skin wounds with alginate-and chitosan-based scaffolds ( Cai and Li, 2020 ; Gaissler et al, 2021 ).…”

Advances in therapeutic nanodrug delivery systems for infectious lung diseases: a review

“…In some studies, CS nanoparticles (CSNPs) have been coupled with bioactive components such as functionally modified peptides [31], cell membranes, cell receptors [32] and metal elements [29,33] to endow them with targeted killing or strong protective abilities. Ding et al [34] have prepared red-blood-cell-hitchhiking nanoparticles (RBC-MPSS-CSNP) by using an ionotropic gelation technique to load methylprednisolone sodium succinate into CSNP and mixed it with red blood cells from the rat abdominal aorta (Figure 1a). RBC-MPSS-CSNPs have a long duration of action in vivo and preferentially accumulate in the lungs, thus facilitating sustained release of drugs to the lungs and overcoming the drawback of the short duration of action of methylprednisolone sodium succinate in vivo (Figure 1b).…”