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A Platform for Enhanced Contrast Ultrasound Targeted Delivery of Therapeutics
Author(s) -
Burke Caitlin Wells,
Price Richard J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.594.2
Subject(s) - microbubbles , nanoparticle , ultrasound , drug delivery , biomedical engineering , biophysics , chemistry , medicine , nanotechnology , materials science , radiology , biology
Recently, there has been considerable interest in examining ultrasound‐mediated microbubble destruction as a method for noninvasive delivery of therapeutics. Here, we tested whether nanoparticle delivery could be markedly improved by ultrasound‐mediated destruction of composite delivery agents comprised of 100nm poly(lactide‐ co ‐glycolide) (PLAGA) nanoparticles that are adhered to 2‐4 μm diameter albumin shelled microbubbles, denoted here as microbubble nanoparticle composite agents (MNCAs). Fluorescently tagged PLAGA nanoparticles were delivered to mouse gracilis muscle via the ultrasonic destruction of circulating MNCAs. Cross‐sections of MNCA treated muscles were compared to muscles treated with microbubbles co‐administered with nanoparticles. We observed a 4‐fold increase in nanoparticle delivery in MNCA treated muscles over muscles treated with a co‐administration. These results suggest that binding the PLAGA nanoparticles to the albumin shell, as opposed to co‐administering them, significantly increases the delivery of nanoparticles to tissue. In preliminary studies using a tumor model in mice, we demonstrated that ultrasound mediated destruction of MNCAs resulted in nanoparticle delivery to tumor tissue. This further supports the utility of these MNCAs for a multitude of targeted drug delivery applications. Supported by the FUSF, the Hartwell Foundation, and NIH HL74082.