Targeted delivery of amikacin into granuloma.
BACKGROUND
Nontuberculous mycobacterial (NTM) infection is a growing problem in the United States and remains underrecognized in the developing world. The management of NTM infections is further complicated by several factors, including the need to use high systemic doses of toxic agents, the length of therapy, and the development of drug resistance.


OBJECTIVE
We have evaluated the use of monocyte-derived dendritic cells (DCs) as a delivery vehicle for a luminescent derivative of amikacin prepared by conjugation to fluorescein isothiocyanate (FITC) (amikacin-FITC) into granulomas formed in the tissues of mice infected with Mycobacterium avium.


METHODS
Amikacin-FITC was prepared and quantitative fluorescence was used to track the intracellular uptake of this modified antibiotic. The antibiotic activity of amikacin-FITC was also determined to be comparable to unmodified amikacin against M. avium. Amikacin-FITC-loaded DCs were first primed with M. avium, and then the cells were injected into the tail vein of infected mice. After 24 hours, the mice were sacrificed and the tissues were analyzed under fluorescence microscope.


RESULTS
We found that we were able to deliver amikacin into granulomas in a mouse model of disseminated mycobacterial infection. No increase in levels of monocyte chemoattractant protein-1 and its CCR2 as markers of inflammation were found when DCs were treated with amikacin-FITC.


CONCLUSIONS
DC-based drug delivery may be an adjunct and useful method of delivering high local concentrations of antibiotics into mycobacterial granulomas.
Montes-Worboys
Ana
A
University of Florida, Gainesville, 32610-0225, USA.
Brown
Scott
S
Regev
Doron
D
Bellew
Brendan F
BF
Mohammed
Kamal A
KA
Faruqi
Ibrahim
I
Sharma
Parvesh
P
Moudgil
Brij
B
Antony
Veena B
VB
D000583:Amikacin / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006099:Granuloma / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D009162:Mycobacterium avium / Q000302:isolation & purification; D009374:Neoplasms, Experimental
D000900:Anti-Bacterial Agents; D000583:Amikacin