Journal
JOURNAL OF CONTROLLED RELEASE
Volume 203, Issue -, Pages 140-149Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2015.02.016
Keywords
Lipoplex; Alveolar type II cell; Surfactant protein-C; MicroRNA; Targeted delivery
Funding
- Ohio State University Howard Hughes Medical Institute Med-to-Grad Training Program
- Ohio State University Pelotonia Idea Award Program
- National Heart Lung and Blood Institute at National Institutes of Health [R01-HL102469]
- State University of New York at Buffalo Start Up fund
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL102469] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Alveolar type II (ATII) respiratory epithelial cells are essential to normal lung function. They may be also central to the pathogenesis of diseases such as acute lung injury, pulmonary fibrosis, and pulmonary adenocarcinoma. Hence, ATII cells are important therapeutic targets. However, effective ATII cell-specific drug delivery in vivo requires carriers of an appropriate size, which can cross the hydrophobic alveolar surfactant film and polar aqueous layer overlying ATII cells, and be taken up without inducing ATII cell dysfunction, pulmonary inflammation, lung damage, or excessive systemic spread and side-effects. We have developed lipoplexes as a versatile nanoparticle carrier system for drug/RNA delivery. To optimize their pulmonary localization and ATII cell specificity, lipoplexes were conjugated to an antibody directed against the ATII cell-specific antigen surfactant protein-C (SP-C) then administered to C57BL/6mice via the nares. Intranasally-administered, anti-SP-C-conjugated lipoplexes targeted mouse ATII cells with > 70% specificity in vivo, were retained within ATII cells for at least 48 h, and did not accumulate at significant levels in other lung cell types or viscera. 48 h after treatment with anti-SP-C-conjugated lipoplexes containing the test microRNA miR-486, expression of mature miR-486 was approximately 4-fold higher in ATII cells than whole lung by qRT-PCR, and was undetectable in other viscera. Lipoplexes induced no weight loss, hypoxemia, lung dysfunction, pulmonary edema, or pulmonary inflammation over a 6-day period. These findings indicate that ATII cell-targeted lipoplexes exhibit all the desired characteristics of an effective drug delivery system for the treatment of pulmonary diseases that result primarily from ATII cell dysfunction. (C) 2015 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available