Abstract
In order to propose non-ionic surfactant vesicles (niosomes) for the treatment of intracellular infections, a remote loading method (active drug encapsulation) followed by sonication was used to prepare nano-niosome formulations containing ciprofloxacin (CPFX). Size analysis, size distribution and zeta potentials of niosomes were evaluated and then their antimicrobial activity, cellular uptake, cytotoxicity, intracellular distribution, and antibacterial activity against intracellular Staphylococcus aureus infection of murine macrophage-like, J774, cells were investigated in comparison to free drug. Our findings reveal that size and composition of the niosome formula can influence their in vitro biological properties. Vesicles in the 300–600 nm size range were phagocytosed to a greater degree by macrophages in comparison to other size vesicles. The minimum inhibitory concentrations (MICs) of CPFX-loaded niosomes were two to eightfold lower than MICs of free CPFX. In addition, niosome encapsulation of CPFX provided high intracellular antimicrobial activities while free CPFX is ineffective for eradicating intracellular forms of S. aureus. Encapsulation of CPFX in niosomes generally decreased its in vitro cytotoxicity. Our results show that niosomes are suitable drug delivery systems with good efficacy and safety properties to be proposed for drug targeting against intracellular infections.
Similar content being viewed by others
References
Abdelbary G, El-gendy N (2008) Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech 9(3):740–747
Baillie A, Florence A, Hume L, Muirhead G, Rogerson A (1985) The preparation and properties of niosomes—non-ionic surfactant vesicles. J Pharm Pharmacol 37(12):863–868
Bhaskaran S, Panigrahi L (2002) Formulation and evaluation of niosomes using different non-ionic surfactants. Indian J Pharm Sci 64(1):63–65
Caracciolo G, Pozzi D, Caminiti R, Marianecci C, Moglioni S, Carafa M, Amenitsch H (2008) Effect of hydration on the structure of solid-supported niosomal membranes investigated by in situ energy dispersive X-ray diffraction. Chem Phys Lett 462(4):307–312
Champion JA, Walker A, Mitragotri S (2008) Role of particle size in phagocytosis of polymeric microspheres. Pharm Res 25(8):1815–1821
Chono S, Tauchi Y, Morimoto K (2006) Influence of particle size on the distributions of liposomes to atherosclerotic lesions in mice. Drug Dev Ind Pharm 32(1):125–135
Chono S, Tanino T, Seki T, Morimoto K (2007) Uptake characteristics of liposomes by rat alveolar macrophages: influence of particle size and surface mannose modification. J Pharm Pharmacol 59(1):75–80
Ellbogen MH, Olsen KM, Gentry-Nielsen MJ, Preheim LC (2003) Efficacy of liposome-encapsulated ciprofloxacin compared with ciprofloxacin and ceftriaxone in a rat model of Pneumococcal pneumonia. J Antimicrob Chemother 51(1):83–91
Epstein-Barash H, Gutman D, Markovsky E, Mishan-Eisenberg G, Koroukhov N, Szebeni J, Golomb G (2010) Physicochemical parameters affecting liposomal bisphosphonates bioactivity for restenosis therapy: internalization, cell inhibition, activation of cytokines and complement, and mechanism of cell death. J Controlled Release 146(2):182–195
Goyal P, Goyal K, Kumar SGV, Singh A, Katare OP, Mishra DN (2005) Liposomal drug delivery systems—clinical applications. Acta Pharm 55(1):1–25
Gubernator J, Drulis-Kawa Z, Dorotkiewicz-Jach A, Doroszkiewicz W, Kozubek A (2007) In vitro antimicrobial activity of liposomes containing ciprofloxacin, meropenem and gentamicin against Gram-negative clinical bacterial strains. Lett Drug Des Discov 4(4):297–304
Hamrick TS, Diaz AH, Havell EA, Horton JR, Orndorff PE (2003) Influence of extracellular bactericidal agents on bacteria within macrophages. Infect Immun 71(2):1016–1019
Hernández-Borrell J, Montero MT (2003) Does ciprofloxacin interact with neutral bilayers? An aspect related to its antimicrobial activity. Int J Pharm 252(1–2):149–157
Hofmann T (2012) New developments in inhaled antibiotics for the treatment of Pseudomonas aeruginosa. Curr Pharm Des 18(5):683–695
Holmes B, Quie PG, Windhorst DB, Pollara B, Good RA (1966) Protection of phagocytized bacteria from the killing action of antibiotics. Nature 210(5041):1131
Junyaprasert VB, Teeranachaideekul V, Supaperm T (2008) Effect of charged and non-ionic membrane additives on physicochemical properties and stability of niosomes. AAPS PharmSciTech 9(3):851–859
Kaufmann SHE (2011) Intracellular pathogens: living in an extreme environment. Immunol Rev 240(1):5–10
Lawrence JW, Claire DC, Weissig V, Rowe TC (1996) Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells. Mol Pharmacol 50(5):1178
Lee SC, Lee KE, Kim JJ, Lim SH (2005) The effect of cholesterol in the liposome bilayer on the stabilization of incorporated retinol. J Liposome Res 15(3–4):157–166
Maurin M, Raoult D (1996) Optimum treatment of intracellular infection. Drugs 52(1):45
Moazeni E, Gilani K, Sotoudegan F, Pardakhty A, Najafabadi AR, Ghalandari R, Fazeli MR, Jamalifar H (2010) Formulation and in vitro evaluation of ciprofloxacin containing niosomes for pulmonary delivery. J Microencapsul 27(7):618–627
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63
Mullaicharam A, Murthy R (2004) Lung accumulation of niosome-entrapped rifampicin following intravenous and intratracheal administration in the rat. STP Pharm Sci 14(2):99–104
Mullaicharam A, Murthy R (2006) Lung accumulation of niosome-entrapped gentamicin sulfate follows intravenous and intratracheal administration in rats. J Drug Deliv Sci Technol 16(2):109–113
Naresh RAR, Udupa N, Devi P (1996) Niosomal plumbagin with reduced toxicity and improved anticancer activity in BALB/C mice. J Pharm Pharmacol 48(11):1128–1132
Oh YK, Nix DE, Straubinger RM (1995) Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection. Antimicrob Agents Chemother 39(9):2104–2111
Pandey VP, Deivasigamani K (2009) Preparation and characterization of ofloxacin non-ionic surfactant vesicles for ophthalmic use. J Pharm Res 2(7):1330–1334
Pardakhty A, Foroumadi A, Hashemi M, Rajabalian S, Heidari MR (2007) In vitro cytotoxicity and phototoxicity of N-piperazinyl quinoline derivatives with a 2-thienyl group. Toxicol In Vitro 21(6):1031–1038
Rani NP, Suriyaprakash TNK, Senthamarai R (2010) Formulation and evaluation of rifampicin and gatifloxacin niosomes on logarithmic-phase cultures of Mycobacterium tuberculosis. Int J Pharm Biol Sci 1:379–387
Rous P, Jones F (1916) The protection of pathogenic microorganisms by living tissue cells. J Exp Med 23(5):601
Sadeghi-Aliabadi H, Sajjadi SE, Khodamoradi M (2009) Cytotoxicity of Euphorbia macroclada on MDA-MB-468 breast cancer cell line. Iran J Pharm Sci 5(2):103–108
Shahiwala A, Misra A (2002) Studies in topical application of niosomally entrapped Nimesulide. J Pharm Pharm Sci 5(3):220
Varshosaz J, Pardakhty A, Hajhashemi V, Najafabadi AR (2003) Development and physical characterization of sorbitan monoester niosomes for insulin oral delivery. Drug Delivery 10(4):251–262
Wong JP, Yang H, Blasetti KL, Schnell G, Conley J, Schofield LN (2003) Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection. J Controlled Release 92(3):265–273
Zaru M, Sinico C, De Logu A, Caddeo C, Lai F, Manca ML, Fadda AM (2009) Rifampicin-loaded liposomes for the passive targeting to alveolar macrophages: in vitro and in vivo evaluation. J Liposome Res 19(1):68–76
Acknowledgments
This study was financially supported by Isfahan University of Medical Sciences (Grant No. 188097).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Akbari, V., Abedi, D., Pardakhty, A. et al. Ciprofloxacin nano-niosomes for targeting intracellular infections: an in vitro evaluation. J Nanopart Res 15, 1556 (2013). https://doi.org/10.1007/s11051-013-1556-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11051-013-1556-y