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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Y. Ishibashi and T. Arai. Specific inhibition of phagosome-lysosome fusion in murine macrophages mediated by Salmonella typhimurium infection. FEMS Microbiol. Immunol. 64:35–44 (1990).
N. A. Buchmeier and F. Heffron. Inhibition of macrophage phagosome-lysosome fusion by Salmonella typhimurium. Infect. Immun. 59:2232–2238 (1991).
M. E. W. Carrol, P. S. Jackett, V. R. Aber, and D. B. Lowrie. Phagolysosome formation, cyclic adenosine 3′:5′-monophosphate and the fate of Salmonella typhimurium within mouse peritoneal macrophages. J. Gen. Microbiol. 110:421–429 (1979).
I. A. J. M. Bakker-Woudenberg, P. de Bos, W. B. van Leeuwen, and M. F. Michel. Efficacy of ampicillin therapy in experimental listeriosis in mice with impaired T-cell-mediated immune response. Antimicrob. Agents Chemother. 19:76–81 (1981).
C. Renard, H. J. Vanderhaeghe, P. J. Claes, A. Zenebergh, and P. M. Tulkens. Influence of conversion of penicillin G into a basic derivative on its accumulation and subcellular localization in cultured macrophages. Antimicrob. Agents Chemother. 31:410–416 (1987).
P. Couvreur. Polyalkylcyanoacrylates as colloidal drugs carriers. In Crit. Rev. Ther. Drug Carrier Sys. 5:1–20 (1988).
P. Couvreur, B. Kante, and M. Roland. Les vecteurs lysosomotropes. J. Pharm. Belg. 35:51–60 (1980).
P. Couvreur, L. Grislain, V. Lenaerts, F. Brasseur, P. Guiot, and A. Biernacki. Biodegradable polymeric nanoparticles as drug carrier for antitumor agents. In P. Guiot and P. Couvreur, (eds.), Polymeric Nanoparticles and Microspheres, CRC Press, Boca Raton, FL, 1986, pp. 27–93.
C. R. Alving. Macrophages as targets for delivery of liposome-encapsulated antimicrobial agents. Adv. Drug Deliv. Rev. 2:107–128 (1988).
J. V. Desiderio and S. G. Campbell. Liposome-encapsulated cephalothin in the treatment of experimental murine salmonellosis. J. Reticuloendothel. Soc. 34:279–287 (1983).
C. E. Swenson, K. A. Stewart, J. L. Hammet, W. E. Fitzsimmons, and R. S. Ginsberg. Pharmacokinetics and in vivo activity of liposome-encapsulated gentamicin. Antimicrob. Agents Chemother. 34:235–240 (1990).
E. Fattal, J. Rojas, L. Roblot-Treupel, A. Andremont, and P. Couvreur. Ampicillin-loaded liposomes and nanoparticles: Comparison of drug loading, drug release and in vitro antimicrobial activity. J. Microencaps. 8:29–36 (1991).
E. Fattal, M. Youssef, P. Couvreur, and A. Andremont. Treatment of experimental salmonellosis in mice with ampicillinbound nanoparticles. Antimicrob. Agents Chemother. 33:1540–1543 (1989).
J. S. Weldon, J. F. Munnell, W. L. Hanson, and C. R. Alving. Liposomal chemotherapy in visceral leishmaniasis: An ultrastructural study of an intracellular pathway. Z. Parasitenkd. 69:415–424 (1983).
S. Majumdar, D. Flasher, D. S. Friend, P. Nassos, D. Yajko, W. K. Hadley, and N. Düzgünes. Efficacies of liposome-encapsulated streptomycin and ciprofloxacin against Mycobacterium avium-M. intracellulare complex infections in human peripheral monocyte/macrophages. Antimicrob. Agents Chemother. 36:2808–2815 (1992).
V. Guise, P. Jaffray, J. Delattre, F. Puisieux, M. Adolphe, and P. Couvreur. Comparative cell uptake of propidium iodide associated with liposomes or nanoparticles. Cell. Mol. Biol. 33:397–405 (1987).
P. Couvreur, M. Roland, and P. Speiser. Biodegradable submicroscopic particles containing a biologically active substance and compositions containing them. U.S. Patent No. 4.329.332 (1982).
S. Henry-Michelland, M. J. Alonso, A. Andremont, P. Maincent, J. Sauzières, and P. Couvreur. Attachment of antibiotics to nanoparticles: Preparation, drug release and antimicrobial activity in vitro. Int. J. Pharm. 35:121–127 (1987).
T. B. Vree, Y. A. Hekster, A. M. Baars, and E. Van der Kleijn. Rapid determination of amoxycillin (Clamoxyl) and ampicillin (Penbritin) in body fluids of many by means of high-performance liquid chromatography. J. Chromatogr. 145:469–501 (1978).
O. Balland, H. Pinto-Alphandary, S. Pecquet, A. Andremont, and P. Couvreur. Intracellular uptake and activity of ampicillinloaded nanoparticles on murine macrophages infected by Salmonella typhimurium J. Antimicrob. Chemother. (in press).
R. Bacallao, M. Bomsel, E. H. K. Stelzer, and J. De Mey. Guiding principles of specimen preservation for confocal fluorescence microscopy. In J. B. Pawley (ed.), Handbook of Biological Confocal Microscopy, Plenum Press, New York and London, 1990, pp. 197–205.
V. Lenaerts, P. Couvreur, D. Christiaens-Leyh, E. Joiris, M. Roland, B. Rollman, and P. Speiser. Degradation of poly(isobutylcyanoacrylate) nanoparticles. Biomaterials 5:65–68 (1984).
R. Whitehouse, J. C. Benichou, and A. Ryter. Procedure for longitudinal orientation of rodshaped bacteria and the production of a high cell density of procaryotic and eucaryotic cells in thin sections for electron microscopy. Biol. Cell. 30:155–178 (1977).
B. Seijo, E. Fattal, L. Roblot-Treupel, and P. Couvreur. Design of nanoparticles of less than 50 nm in diameter. Preparation, characterization and drug loading. Int. J. Pharm. 62:1–7 (1990).
S. J. Douglas, L. Illum, and S. S. Davis. Particle size and size distribution of poly (butyl 2-cyanoacrylate) nanoparticles. II. Influence of stabilizers. J. Colloid Interface Sci. 103:154–163 (1985).
J. L. Grangier, M. Puygrenier, J. C. Gautier, and P. Couvreur. Nanoparticles as carriers for growth hormone releasing factor. J. Control. Release 15:3–13 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pinto-Alphandary, H., Balland, O., Laurent, M. et al. Intracellular Visualization of Ampicillin-Loaded Nanoparticles in Peritoneal Macrophages Infected in Vitro with Salmonella typhimurium . Pharm Res 11, 38–46 (1994). https://doi.org/10.1023/A:1018985308984
Issue Date:
DOI: https://doi.org/10.1023/A:1018985308984