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Ciprofloxacin nano-niosomes for targeting intracellular infections: an in vitro evaluation

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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.

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References

  • Abdelbary G, El-gendy N (2008) Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech 9(3):740–747

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Bhaskaran S, Panigrahi L (2002) Formulation and evaluation of niosomes using different non-ionic surfactants. Indian J Pharm Sci 64(1):63–65

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Champion JA, Walker A, Mitragotri S (2008) Role of particle size in phagocytosis of polymeric microspheres. Pharm Res 25(8):1815–1821

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Hofmann T (2012) New developments in inhaled antibiotics for the treatment of Pseudomonas aeruginosa. Curr Pharm Des 18(5):683–695

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Kaufmann SHE (2011) Intracellular pathogens: living in an extreme environment. Immunol Rev 240(1):5–10

    Article  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Maurin M, Raoult D (1996) Optimum treatment of intracellular infection. Drugs 52(1):45

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Pandey VP, Deivasigamani K (2009) Preparation and characterization of ofloxacin non-ionic surfactant vesicles for ophthalmic use. J Pharm Res 2(7):1330–1334

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Rous P, Jones F (1916) The protection of pathogenic microorganisms by living tissue cells. J Exp Med 23(5):601

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • Shahiwala A, Misra A (2002) Studies in topical application of niosomally entrapped Nimesulide. J Pharm Pharm Sci 5(3):220

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

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Acknowledgments

This study was financially supported by Isfahan University of Medical Sciences (Grant No. 188097).

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Correspondence to Hojjat Sadeghi-Aliabadi.

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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

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  • DOI: https://doi.org/10.1007/s11051-013-1556-y

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