Pulmonary Manifestations of Systemic Disease: Mechanisms of Pulmonary Fibrosis |

Surfactant Protein-A Nanobody-Conjugated Liposomes Loaded With Methylprednisolone for Lung Targeting and Therapeutic Effect for Acute Lung Injury FREE TO VIEW

Huiping Li, MD
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Shanghai Pulmonary Hospital, Shanghai, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A454. doi:10.1016/j.chest.2016.02.473
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SESSION TITLE: Mechanisms of Pulmonary Fibrosis

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, April 17, 2016 at 09:45 AM - 11:15 AM

PURPOSE: To develop a lung-targeting glucocorticoid that could exert its function mainly in the lung tissues, thereby reducing the toxic side effects on other organs.

METHODS: Methylprednisolone (MPS) was used as the treatment drug, and nano-sterically stabilized liposomes (NSSLs) were used as carriers to form the MPS-NSSLs particle. The MPS-NSSLs particle was further conjugated to nanobodies of surfactant protein A (SPANb) to make MPS-NSSLs-SPANb. The characteristics of MPS-NSSLs-SPANb particles were evaluated. Small animal imaging was performed in nude mice to analyze the distribution of MPS-NSSLs-SPANb in vivo, and the content of MPS in the different organs of rats was measured at different time points to verify the lung-targeting property of MPS-NSSLs-SPANb. The safety and therapeutic effect of MPS-NSSLs-SPANb were evaluated in rats with bleomycin-induced lung injury.

RESULTS: 1) The diameter of MPS-NSSLs-SPANb particles was 105.8 ± 0.8 nm, the encapsulation efficiency of NSSLs-SPANb to MPS was 92.5 ± 0.3%. MPS-NSSLs-SPANb could be stored at 4°C for no less than 12 weeks. 2) ELISA showed that MPS-NSSLs-SPANb could actively bind with SP-A antigen. Small animal imaging and pharmacokinetic study of MPS-NSSLs-SPANb in rats showed that the peak value of MPS in lung after MPS-NSSLs-SPANb injection was 4.58-fold (Ce = 4.58) of that after MPS injection, and the AUC0-12h after MPS-NSSLs-SPANb injection was 17.78-fold (Re = 17.78) of that after MPS injection, indicating that MPS-NSSLs-SPANb had good lung-targeting properties. 3) In rats with bleomycin-induced lung injury, MPS-NSSLs-SPANb significantly reduced the level of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid (BALF) and the expression of NK-κB in the lung tissues, thereby alleviating the injuries of the lung and increasing the survival proportion of rats after lung damage.

CONCLUSIONS: This study for the first time developed a lung-targeting glucocorticoid (MPS-NSSLs-SPANb) using SP-A nanobody as the lung-targeting molecule, which was more effective in treating rats with bleomycin-induced lung injury.

CLINICAL IMPLICATIONS: This novel drug MPS-NSSLs-SPANb is the first lung-targeting glucocorticoid, which provides new idea and new drug with high effective and low adverse effect for therapy of acute lung injury

DISCLOSURE: The following authors have nothing to disclose: Huiping Li

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