Number of the records: 1
Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics
- 1.0507773 - ÚOCHB 2020 RIV US eng J - Journal Article
Crooke, S. N. - Schimer, Jiří - Raji, I. - Wu, B. - Oyelere, A. K. - Finn, M. G.
Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics.
Molecular Pharmaceutics. Roč. 16, č. 7 (2019), s. 2947-2955. ISSN 1543-8384. E-ISSN 1543-8392
Institutional support: RVO:61388963
Keywords : macrophage * macrolide * virus-like particles * azithromycin * clarithromycin * lung targeting
OECD category: Biochemistry and molecular biology
Impact factor: 4.321, year: 2019
Method of publishing: Limited access
https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00180
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.
Permanent Link: http://hdl.handle.net/11104/0298743
Number of the records: 1