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Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: Pulmonary compatible and site-specific drug delivery in lung metastases

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Title Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: Pulmonary compatible and site-specific drug delivery in lung metastases
 
Creator JOSHI, N
SHIRSATH, N
SINGH, A
JOSHI, KS
BANERJEE, R
 
Subject SILICA NANOPARTICLES
LIPOSOME AEROSOL
PACLITAXEL
TOXICITY
MICE
CELLS
MECHANISMS
INHIBITION
CANCER
CAMPTOTHECIN
 
Description Concerns related to pulmonary toxicity and non-specificity of nanoparticles have limited their clinical applications for aerosol delivery of chemotherapeutics in lung cancer. We hypothesized that pulmonary surfactant mimetic nanoparticles that offer pH responsive release specifically in tumor may be a possible solution to overcome these issues. We therefore developed lung surfactant mimetic and pH responsive lipid nanovesicles for aerosol delivery of paclitaxel in metastatic lung cancer. 100-200 nm sized nanovesicles showed improved fusogenicity and cytosolic drug release, specifically with cancer cells, thereby resulting in improved cytotoxicity of paclitaxel in B16F10 murine melanoma cells and cytocompatibility with normal lung fibroblasts (MRC 5). The nanovesicles showed airway patency similar to that of endogenous pulmonary surfactant and did not elicit inflammatory response in alveolar macrophages. Their aerosol administration while significantly improving the biodistribution of paclitaxel in comparison to Taxol (R) (i.v.), also showed significantly higher metastastes inhibition (similar to 75%) in comparison to that of i.v. Taxol (R) and i.v. Abraxane (R). No signs of interstitial pulmonary fiborisis, chronic inflammation and any other pulmonary toxicity were observed with nanovesicle formulation. Overall, these nanovesicles may be a potential platform to efficiently deliver hydrophobic drugs as aerosol in metastatic lung cancer and other lung diseases, without causing pulmonary toxicity.
 
Publisher NATURE PUBLISHING GROUP
 
Date 2014-12-29T05:59:44Z
2014-12-29T05:59:44Z
2014
 
Type Article
 
Identifier SCIENTIFIC REPORTS, 4
2045-2322
http://dx.doi.org/10.1038/srep07085
http://dspace.library.iitb.ac.in/jspui/handle/100/17255
 
Language English