The Construction Of Targeted Methylprednisolone Nano Liposomes In People Lung Tissue

Objectives: To create a novel glucocorticoid preparation, which is low immunogenic and lung targeting, by conjugating humanized Surfactant Protein A Nano antibody(SPANb) and methylprednisolone loaded liposome. That could promote the curative effect and reduce the side reactions.Methods:1) To create a methylprednisolone loaded liposome. Then Methylprednisolone Nano-Sterically Stable Liposomes(MPS-NSSLs) were evaluated by size distribution, morphology under Cryogenic Transmission Electron Microscopy(Cryo-TEM), drug envelopment rate, and stability.2) To create a novel glucocorticoid preparation, by conjugating humanized SPANb and methylprednisolone loaded liposome. After conjugation, methylprednisolone loaded liposomes conjugated with SPANb(MPS-NSSLs-SPANb) was evaluated by size, distribution, morphology, drug envelopment rate and stability.3) To observed MPS-NSSLs-SPANb lung targeting in vitro by immunohistochemistry technique. To test the tissue targeting ability of MPS-NSSLs-SPANb, which was achieved by the small animal imaging test and MPS distribution in rats after intravenous injection of MPS-NSSLs-SPANb.Results: 1) MPS drug envelopment rate was 90.7±0.34%.MPS-NSSLs can be stored at 4 ℃ for at least 12 weeks. The size distribution of MPS-NSSLs was about 108.4±0.4nm,with beautiful round shape under Cryo-TEM.2) The particle diameter of MPS-NSSLs-SPANb was around 119.1±0.2nm, with beautiful round shape under Cryo-TEM.3)ELISA test showed good specific binding affinity between the MPS-NSSLs-SPANb and SP-A antigen. MPS-NSSLs-SPANb could bind with human lung tissue specific by the immunohistochemistry, Both small animal imaging test and bio-distribution experiment showed that after injecting MPS-NSSLs-SPANb into rats, the peak concentration of MPS was 3.96 times(Ce=3.96) more than that of MPS injection group. The area under 12 hour concentration-time curve was 9.34 times(Re=9.34) more than that of MPS injection group, which showed a highly specific targeting binding affinity to lung tissues.Conclusions: We first created a humanized SP-A Nano antibody conjugated GCs loaded liposome targeting human lung tissue, which can highly specific bind to human lung tissue. This novel glucocorticoid preparation has great prospect of clinical application.