Targeted renal therapies through microbubbles and ultrasound

• Published in: Advanced drug delivery reviews Vol. 62; no. 14; pp. 1369 - 1377
• Main Authors: Deelman, Leo E., Declèves, Anne-Emilie, Rychak, Joshua J., Sharma, Kumar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-11-2010
• Subjects: Animals; Antibodies; Bioeffects; Contrast agents; Contrast Media; Drug delivery; Drug Delivery Systems; Gene Transfer Techniques; Genetic Therapy; Humans; Injections, Intravenous; Kidney; Kidney - metabolism; Kidney - physiopathology; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Kidney Diseases - therapy; Microbubbles; Molecular imaging; Rabbits; Rats; Swine; Targeted microbubbles; Ultrasonics; Ultrasound; VEGFR2; Molecular imaging; PS; TGF-ß; Targeted microbubbles; VEGF; Bioeffects; ICAM-1; Drug delivery; Kidney; Contrast agents; VCAM-1; PEG; Microbubbles; MadCam-1; MI; Ultrasound; PET
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2010.10.002

Microbubbles and ultrasound enhance the cellular uptake of drugs (including gene constructs) into the kidney. Microbubble induced modifications to the size selectivity of the filtration capacity of the kidney may enable drugs to enter previously inaccessible compartments of the kidney. So far, negative renal side-effects such as capillary bleeding have been reported only in rats, with no apparent damage in larger models such as pigs and rabbits.
Although local delivery is accomplished by applying ultrasound only to the target area, efficient delivery using conventional microbubbles has depended on the combined injection of both drugs and microbubbles directly into the renal artery. Conjugation of antibodies to the shell of microbubbles allows for the specific accumulation of microbubbles in the target tissue after intravenous injection. This exciting approach opens new possibilities for both drug delivery and diagnostic ultrasound imaging in the kidney.