Development and assessment of the efficacy and safety of human lung-targeting liposomal methylprednisolone crosslinked with nanobody

Drug Deliv. 2021 Dec;28(1):1419-1431. doi: 10.1080/10717544.2021.1921073.

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

  • Animals
  • Chemistry, Pharmaceutical
  • Drug Carriers / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Liposomes / chemistry
  • Lung / drug effects
  • Male
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / pharmacology*
  • Mice
  • Mice, Nude
  • Pulmonary Surfactant-Associated Protein A / administration & dosage*
  • Pulmonary Surfactant-Associated Protein A / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Single-Domain Antibodies / administration & dosage
  • Single-Domain Antibodies / pharmacology

Substances

  • Drug Carriers
  • Liposomes
  • Pulmonary Surfactant-Associated Protein A
  • Single-Domain Antibodies
  • 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].