Elaboration of Sterically Stabilized Liposomes for S-Nitrosoglutathione Targeting to Macrophages.
S-nitrosoglutathione (GSNO) is a potential therapeutic for infectious disease treatment because of its pivotal role in macrophage-mediated inflammatory responses and host defense in addition to direct antibacterial activities. In this study, sterically stabilized cationic liposomes (SSCL) and sterically stabilized anionic liposomes (SSAL) were developed as nanocarriers for macrophage targeting. Elaborated liposomes were characterized in terms of size, zeta potential, morphology, encapsulation efficiency, in vitro drug release behavior and cytotoxicity. Their versatility in targeting monocytes/macrophages was determined by confocal laser scanning microscopy and transmission electron microscopy. Flow cytometry revealed that cellular uptake of both SSCL and SSAL was governed by several endocytic clathrin- and caveolae-dependent mechanisms. Quantitative assessments of intracellular nitric oxide demonstrated highly efficient uptake of GSNO-loaded SSCL that was twenty-fold higher than that of GSNO-free molecules. GSNO-loaded SSCL displayed strong bacteriostatic effects on Staphylococcus aureus and Pseudomonas aeruginosa, which can be involved in pulmonary infectious diseases. These results reveal the potential of liposomal GSNO as an anti-infective therapeutic due to its macrophage targeting capacity and direct antibacterial effects.
R
R
Diab
A S
AS
Virriat
C
C
Ronzani
S
S
Fontanay
S
S
Grandemange
A
A
Elaissari
B
B
Foliguet
P
P
Maincent
P
P
Leroy
R E
RE
Duvaj
B H
BH
Rihn
O
O
Joubert
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008264:Macrophages / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009574:Nitro Compounds / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D013347:Subcellular Fractions / Q000737:chemistry
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D053769:Nanocapsules; D009574:Nitro Compounds; C116027:S-nitroglutathione; D005978:Glutathione