Novel echogenic drug-immunoliposomes for drug delivery.
OBJECTIVE
We have developed novel echogenic immunoliposomes (ELIPs) that can be antibody-conjugated for the specific highlighting of atheroma and atheroma components. The utility of these agents for regional drug delivery has not been evaluated previously. We chose to use an antibiotic as the prototype drug. The concept that an infectious agent may affect the development and progression of atherosclerosis has stimulated trials on the use of antibiotics for coronary syndromes. However, these agents are given systemically with concomitant problems. Development of an agent for local drug delivery may obviate adverse effects and improve treatment efficacy. The aim of this study was to evaluate the potential of our ELIPs for drug incorporation and to demonstrate efficient drug delivery to cultured cells.


METHODS
Azithromycin was incorporated into the ELIPs during development. Free drug was removed with a Sephadex G-50 column. Acoustic properties were evaluated using an intravascular ultrasound catheter and quantified by computer-assisted videodensitometry. Human umbilical arterial endothelial cells were infected with Chlamydia pneumoniae. Cells were treated with the drug-ELIP complexes, and infection-forming units were counted using fluorescence techniques.


RESULTS
We were able to incorporate a drug into the ELIPs with retention of acoustic properties. The drug-ELIP complex demonstrated effective inhibition of microbial growth in endothelial cells (P < 0.001 vs. empty liposomes and control).


CONCLUSIONS
We have developed a novel acoustic drug-liposomal agent that can deliver drugs to cultured cells. Although in vivo translation is required, this technique has potential for site-specific drug delivery.
Tiukinhoy
Susan D
SD
Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, IL, USA. s-tiukinhoy@northwestern.edu
Khan
Amer A
AA
Huang
Shaoling
S
Klegerman
Melvin E
ME
MacDonald
Robert C
RC
McPherson
David D
DD
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000187:drug effects; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D014470:Umbilical Cord / Q000187:drug effects / Q000382:microbiology
D000900:Anti-Bacterial Agents; D008081:Liposomes; D017963:Azithromycin