Journal
DRUG DELIVERY
Volume 24, Issue 1, Pages 1770-1781Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2017.1402217
Keywords
Acute lung injury; bioconjugation; liposomes; lung-targeted drug delivery; surfactant protein-A
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Funding
- Ministry of Science and Technology of the People's Republic of China [2016YFC1100200, 2016YFC1100204]
- National Science Foundation of China [81730002, 81670055, 81670056, 91442103, 81500052, 81570057]
- Shanghai Hospital Development Center [16CR3054A]
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The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-alpha, IL-8, and TGF-beta 1 in rat bronchoalveolar lavage fluid and the expression of NK-kappa B in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.
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