期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 101, 期 7, 页码 2468-2478出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.23152
关键词
liposomes; gene delivery; blood-brain barrier; nanotechnology; biocompatibility
资金
- Fraternal Order of Eagles grant
We report bifunctional liposomal delivery system, combining transferrin (Tf)-mediated receptor targeting and poly-L-arginine (PR)-facilitated cell penetration, which overcomes the drawback of saturation of delivery. PR was conjugated to the distal end of distearoyl phosphoethanolamine-polyethylene glycol (PEG) 2000 and was incorporated with other phospholipids in chloroform/methanol (2:1) to form PR liposomes using thin-film hydration technique. Tf-PEG phospholipid micelles were incorporated into PR liposomes using postinsertion technique to form Tf-PR liposomes. The bifunctional liposomes demonstrated significantly (p < 0.05) higher cellular uptake by brain endothelial cells (bEnd.3) and about eightfold higher transfection in primary culture of glial cells as compared with the Tf liposomes. Cell viabilities of Tf-conjugated and bifunctional liposomes were not markedly different; however, transport across in vitro blood-brain barrier model improved considerably after dual modification. The study underlines the potential of bifunctional liposomes as high-efficiency and low-toxicity gene delivery system for the treatment of central nervous system disorders. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2468-2478, 2012
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