Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics.
Mol Pharm
; 16(7): 2947-2955, 2019 07 01.
Article
in En
| MEDLINE
| ID: mdl-31244221
ABSTRACT
Macrophage cells are present in high abundance in the lung to intercept invading microorganisms that gain access through airway mucosal surfaces. Several bacterial pathogens have evolved the capacity to evade the innate immune response by establishing infections within pulmonary macrophages upon phagocytosis, leading to prolonged disease. Macrolide antibiotics such as azithromycin and clarithromycin accumulate in phagocytic cells and have been shown to preferentially distribute in tissues where populations of these cells reside. We employed this class of molecules as targeting ligands to direct virus-like particles (VLPs) to lung-resident macrophages. VLP-macrolide conjugates showed enhanced uptake into RAW 264.7 macrophage cells in culture, with azithromycin displaying the greatest effect; distinct differences were also observed for different macrocycle structures and orientations on the particle surface. Activation of macrophage cells was stimulated by particle uptake toward an intermediate activation state, in contrast to previous reports using macrolide-functionalized gold nanorods that stimulated a cytotoxic macrophage response. Attached azithromycin was also able to direct VLPs to the lungs in mice, with significant accumulation within 2 h of systemic injection. These results suggest that this new class of bioconjugate could serve as an effective platform for intracellular drug delivery in the context of pulmonary infections.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Delivery Systems
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Clarithromycin
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Azithromycin
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Capsid Proteins
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Anti-Bacterial Agents
Limits:
Animals
Language:
En
Journal:
Mol Pharm
Journal subject:
BIOLOGIA MOLECULAR
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FARMACIA
/
FARMACOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
United States
Country of publication:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA