Abstract
Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.
Keywords:
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF); humanized surfactant protein-A (hSP-A); humanized surfactant protein-A nanobody (SPANb).
MeSH terms
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Animals
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Chemistry, Pharmaceutical
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Drug Carriers / chemistry
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Enzyme-Linked Immunosorbent Assay
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Humans
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Idiopathic Pulmonary Fibrosis / drug therapy*
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Liposomes / chemistry
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Lung / drug effects
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Male
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Methylprednisolone / administration & dosage*
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Methylprednisolone / pharmacology*
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Mice
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Mice, Nude
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Pulmonary Surfactant-Associated Protein A / administration & dosage*
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Pulmonary Surfactant-Associated Protein A / pharmacology*
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Single-Domain Antibodies / administration & dosage
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Single-Domain Antibodies / pharmacology
Substances
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Drug Carriers
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Liposomes
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Pulmonary Surfactant-Associated Protein A
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Single-Domain Antibodies
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Methylprednisolone
Grants and funding
This study was supported by grants from the National Science Foundation of China [Nos. 81730002, 81670055, 81670056, 91442103, 81500052, and 81570057], Ministry of Science and Technology of the People’s Republic of China [2016YFC1100200, 2016YFC1100204], Shanghai Hospital Development Center [16CR3054A], and National Science & Technology Major Project for Key New Drug Creation and Manufacturing Program [No. 2018ZX09201002-006].