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Passive targeting of phosphatiosomes increases rolipram delivery to the lungs for treatment of acute lung injury: An animal study.
Journal of Controlled Release 2015 September 11
A novel nanovesicle carrier, phosphatiosomes, was developed to enhance the targeting efficiency of phosphodiesterase 4 (PDE4) inhibitor to the lungs for treating acute lung injury (ALI) by intravenous administration. Phosphatiosomes were the basis of a niosomal system containing phosphatidylcholine (PC) and distearoylphosphatidylethanolamine polyethylene glycol (DSPE-PEG). Rolipram was used as the model drug loaded in the phosphatiosomes. Bioimaging, biodistribution, activated neutrophil inhibition, and ALI treatment were performed to evaluate the feasibility of phosphatiosomes as the lung-targeting carriers. An encapsulation percentage of >90% was achieved for rolipram-loaded nanovesicles. The vesicle size and zeta potential of the phosphatiosomes were 154 nm and -34 mV, respectively. Real-time imaging in rats showed a delayed and lower uptake of phosphatiosomes by the liver and spleen. Ex vivo bioimaging demonstrated a high accumulation of phosphatiosomes in the lungs. In vivo biodistribution exhibited increased lung accumulation and reduced brain penetration of rolipram in phosphatiosomes relative to the control solution. Phosphatiosomes improved the lungs/brain ratio of the drug by more than 7-fold. Interaction with pulmonary lipoprotein surfactants and the subsequent aggregation may be the mechanisms for facilitating lung targeting by phosphatiosomes. Rolipram could continue to inhibit active neutrophils after inclusion in the nanovesicles by suppressing O2(-) generation and elevating cAMP. Phosphatiosomes significantly alleviated ALI in mice as revealed by examining their pulmonary appearance, edema, myeloperoxidase (MPO) activity, and histopathology. This study highlights the potential of nanovesicles to deliver the drug for targeting the lungs and attenuating nervous system side effects.
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