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Intracellular visualization of ampicillin-loaded nanoparticles in peritoneal macrophages infected in vitro with
H Pinto-Alphandary1, O Balland, M Laurent
1Laboratoire de Pharmacie Galénique, CNRS, URA 1218, Faculté de Pharmacie, Châtenay-Malabry, France.
Abstract:
Intracellular targeting of ampicillin by means of polyisohexylcyanoacrylate (PIHCA) nanoparticles was studied in murine peritoneal macrophages infected with Salmonella typhimurium. The intracellular distribution of actively endocytosed nanoparticles was visualized by transmission electron microscopy and confocal microscopy. Nanoparticles were either isolated or closely associated with bacteria within phagosomes or phagolysosomes. Thus the potential of ampicillin-loaded nanoparticles in targeting of intracellular bacteria is demonstrated. Consequently, ampicillin, which usually penetrates into cells at a low level, is directly carried in, when loaded on nanoparticles, and brought into contact with intracellular bacteria.
Insights
Polyisohexylcyanoacrylate (PIHCA) nanoparticles effectively deliver ampicillin into macrophages, targeting intracellular Salmonella typhimurium bacteria. This nanoparticle drug delivery system enhances ampicillin
Area of Science:
- Pharmacology
- Nanotechnology
- Microbiology
Background:
- Salmonella typhimurium infections pose challenges due to intracellular bacterial persistence.
- Ampicillin penetration into host cells is often limited, hindering effective treatment of intracellular pathogens.
- Targeted drug delivery systems are needed to improve antibiotic efficacy against intracellular bacteria.
Purpose of the Study:
- To investigate the intracellular targeting of ampicillin using polyisohexylcyanoacrylate (PIHCA) nanoparticles.
- To evaluate the delivery of ampicillin-loaded PIHCA nanoparticles into murine peritoneal macrophages infected with Salmonella typhimurium.
- To assess the distribution of nanoparticles within infected host cells.
Main Methods:
- Murine peritoneal macrophages infected with Salmonella typhimurium were used as a model system.
- Polyisohexylcyanoacrylate (PIHCA) nanoparticles loaded with ampicillin were synthesized and utilized.
- Transmission electron microscopy and confocal microscopy were employed to visualize nanoparticle distribution.
Main Results:
- Actively endocytosed PIHCA nanoparticles were observed within macrophages.
- Nanoparticles were found either isolated or closely associated with Salmonella typhimurium within phagosomes and phagolysosomes.
- This demonstrates successful intracellular delivery of nanoparticles to bacterial infection sites.
Conclusions:
- Ampicillin-loaded PIHCA nanoparticles show potential for targeting intracellular bacteria.
- This nanoparticle-based approach facilitates direct delivery of ampicillin to intracellular pathogens.
- The study highlights a promising strategy for enhancing antibiotic treatment of intracellular infections.