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Published on: December 15, 2010
Targeted delivery of amikacin into granuloma
Ana Montes-Worboys1, Scott Brown, Doron Regev
1University of Florida, Gainesville, 32610-0225, USA.
Rationale:
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.
Objectives:
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.
Measurements And Main 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.
Insights
Dendritic cells (DCs) loaded with amikacin-FITC successfully delivered the antibiotic into granulomas in a mouse model of mycobacterial infection. This novel approach shows promise for treating nontuberculous mycobacterial infections with improved drug delivery.
Area of Science:
- Immunology
- Microbiology
- Drug Delivery Systems
Background:
- Nontuberculous mycobacterial (NTM) infections are a growing global health concern.
- Managing NTM infections is challenging due to toxic drug doses, lengthy treatment, and drug resistance.
- Current treatment strategies require improvement for effective NTM infection management.
Purpose of the Study:
- To evaluate monocyte-derived dendritic cells (DCs) as a delivery vehicle for amikacin.
- To deliver a luminescent amikacin derivative (amikacin-FITC) into granulomas in a mouse model of Mycobacterium avium infection.
- To assess the efficacy of DC-mediated drug delivery for NTM infections.
Main Methods:
- Prepared amikacin-FITC and verified its antibiotic activity against M. avium.
- Loaded amikacin-FITC into DCs, primed them with M. avium, and injected into infected mice.
- Analyzed drug distribution into granulomas using fluorescence microscopy.
Main Results:
- Successfully delivered amikacin-FITC into granulomas in a disseminated mycobacterial infection mouse model.
- Confirmed comparable antibiotic activity of amikacin-FITC to unmodified amikacin.
- Observed no increase in inflammatory markers (monocyte chemoattractant protein-1 and CCR2) with amikacin-FITC-treated DCs.
Conclusions:
- Dendritic cell-based drug delivery is a potential adjunct therapy for NTM infections.
- This method enables high local concentrations of antibiotics within mycobacterial granulomas.
- DC delivery offers a promising strategy to overcome challenges in NTM treatment.
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