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Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

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Abstract

The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 ± 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague–Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

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References

  • Aderem A, Underhill DM (1999) Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17:593–623. doi:10.1146/annurev.immunol.17.1.593

    Article  CAS  Google Scholar 

  • Albrecht C, Scherbart AM, Berlo Dv, Braunbarth CM, Schins RPF, Scheel J (2009) Evaluation of cytotoxic effects and oxidative stress with hydroxyapatite dispersions of different physicochemical properties in rat NR8383 cells and primary macrophages. Toxicol In Vitro 23(3):520–530. doi:10.1016/j.tiv.2009.01.005

    Article  CAS  Google Scholar 

  • Armstrong JA, Arcy Hart PD (1972) Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med 134(3):713–740

    Article  Google Scholar 

  • Bivas-Benita M, Zwier R, Junginger HE, Borchard G (2005) Non-invasive pulmonary aerosol delivery in mice by the endotracheal route. Eur J Pharm Biopharm 61(3):214–218

    Article  CAS  Google Scholar 

  • Bothamley G (2001) Drug treatment for tuberculosis during pregnancy: safety considerations. Drug Saf 24:553–565

    Article  CAS  Google Scholar 

  • Briones E, Isabel Colino C, Lanao JM (2008) Delivery systems to increase the selectivity of antibiotics in phagocytic cells. J Controlled Release 125(3):210–227. doi:10.1016/j.jconrel.2007.10.027

    Article  CAS  Google Scholar 

  • Chellat F, Merhi Y, Moreau A, Yahia LH (2005) Therapeutic potential of nanoparticulate systems for macrophage targeting. Biomaterials 26(35):7260–7275. doi:10.1016/j.biomaterials.2005.05.044

    Article  CAS  Google Scholar 

  • Chen J, Chen Z, Narasaraju T, Jin N, Liu L (2004) Isolation of highly pure alveolar epithelial type I and type II cells from rat lungs. Lab Invest 84(6):727–735

    Article  Google Scholar 

  • Chono S, Tanino T, Seki T, Morimoto K (2006) Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes. J Drug Target 14(8):557–566. doi:10.1080/10611860600834375

    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. doi:10.1211/jpp.59.1.0010

    Article  CAS  Google Scholar 

  • Chono S, Tanino T, Seki T, Morimoto K (2008) Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections. J Controlled Release 127(1):50–58. doi:10.1016/j.jconrel.2007.12.011

    Article  CAS  Google Scholar 

  • Chuan JL, Gong T, Sun X, Zhang Z (2011) Preparation of rifampicin-solid lipid nanoparticles and evaluation of their cell specificity. West China J Pharm Sci 26(3):223–225

    CAS  Google Scholar 

  • Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422(6927):37–44. doi:10.1038/nature01451

    Article  CAS  Google Scholar 

  • Crofton John (1960) Drug treatment of tuberculosisl. BMJ 2:370–373

    Article  CAS  Google Scholar 

  • Edelson JD, Shannon JM, Mason RJ (1988) Alkaline phosphatase: a marker of alveolar type II cell differentiation. Am J Respir Crit Care Med 138(5):1268–1275. doi:10.1164/ajrccm/138.5.1268

    Article  CAS  Google Scholar 

  • Ferrari G, Langen H, Naito M, Pieters J (1999) A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell 97(4):435–447. doi:10.1016/s0092-8674(00)80754-0

    Article  CAS  Google Scholar 

  • He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31(13):3657–3666. doi:10.1016/j.biomaterials.2010.01.065

    Article  CAS  Google Scholar 

  • Hirota K, Hasegawa T, Hinata H, Ito F, Inagawa H, Kochi C, Soma G-I, Makino K, Terada H (2007) Optimum conditions for efficient phagocytosis of rifampicin-loaded PLGA microspheres by alveolar macrophages. J Controlled Release 119(1):69–76. doi:10.1016/j.jconrel.2007.01.013

    Article  CAS  Google Scholar 

  • Hirota K, Hasegawa T, Nakajima T, Inagawa H, Kohchi C, Soma G-I, Makino K, Terada H (2010) Delivery of rifampicin–PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis. J Controlled Release 142(3):339–346. doi:10.1016/j.jconrel.2009.11.020

    Article  CAS  Google Scholar 

  • Krist LFG, Kerremans M, Koenen H, Blijleven N, Eestermans IL, Calame W, Meyer S, Beelen RHJ (1995) Novel isolation and purification method permitting functional cytotoxicity studies of macrophages from milky spots in the greater omentum. J Immunol Methods 184(2):253–261. doi:10.1016/0022-1759(95)00096-s

    Article  CAS  Google Scholar 

  • Lawlor C, Kelly C, O’Leary S, O’Sullivan MP, Gallagher PJ, Keane J, Cryan SA (2011) Cellular targeting and trafficking of drug delivery systems for the prevention and treatment of MTb. Tuberculosis 91(1):93–97. doi:10.1016/j.tube.2010.12.001

    Article  CAS  Google Scholar 

  • Li Y-Z, Sun X, Gong T, Liu J, Zuo J, Zhang Z-R (2010) Inhalable microparticles as carriers for pulmonary delivery of thymopentin-loaded solid lipid nanoparticles. Pharm Res 27(9):1977–1986. doi:10.1007/s11095-010-0201-z

    Article  CAS  Google Scholar 

  • McKinney J, Hoener zu Bentrup K, Munoz-Elias E, Chan WT, Swensonēǵ D, Sacchettinik J (2000) Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406(6797):735–738

    Article  CAS  Google Scholar 

  • Nafee N, Schneider M, Schaefer UF, Lehr C-M (2009) Relevance of the colloidal stability of chitosan/PLGA nanoparticles on their cytotoxicity profile. Int J Pharm 381(2):130–139. doi:10.1016/j.ijpharm.2009.04.049

    Article  CAS  Google Scholar 

  • Natarajan K, Kundu M, Sharma P, Basu J (2011) Innate immune responses to M. tuberculosis infection. Tuberculosis 91(5):427–431. doi:10.1016/j.tube.2011.04.003

    Article  CAS  Google Scholar 

  • Nguyen L, Pieters J (2005) The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages. Trends Cell Biol 15(5):269–276. doi:10.1016/j.tcb.2005.03.009

    Article  CAS  Google Scholar 

  • Onoshita T, Shimizu Y, Yamaya N, Miyazaki M, Yokoyama M, Fujiwara N, Nakajima T, Makino K, Terada H, Haga M (2010) The behavior of PLGA microspheres containing rifampicin in alveolar macrophages. Colloids Surf B 76(1):151–157. doi:10.1016/j.colsurfb.2009.10.036

    Article  CAS  Google Scholar 

  • Pallanza R, Arioli V, Furesz S, Bolzoni G (1967) Rifampicin: a new rifamycin. II. Laboratory studies on the antituberculous activity and preliminary clinical observations. Arzneimittelforschung 17(5):529–534

    CAS  Google Scholar 

  • Panchagnula R, Sood A, Sharda N, Kaur K, Kaul CL (1999) Determination of rifampicin and its main metabolite in plasma and urine in presence of pyrazinamide and isoniazid by HPLC method. J Pharm Biomed Anal 18(6):1013–1020. doi:10.1016/s0731-7085(98)00112-5

    Article  CAS  Google Scholar 

  • Pandey R, Khuller GK (2005) Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. Tuberculosis 85(4):227–234. doi:10.1016/j.tube.2004.11.003

    Article  CAS  Google Scholar 

  • Pandey R, Sharma S, Khuller G (2005) Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis 85(5–6):415–420. doi:10.1016/j.tube.2005.08.009

    Article  CAS  Google Scholar 

  • Post M, Smith BT (1988) Histochemical and immunocytochemical identification of alveolar type II epithelial cells isolated from fetal rat lung. Am J Respir Crit Care Med 137(3):525–530. doi:10.1164/ajrccm/137.3.525

    Article  CAS  Google Scholar 

  • Thomas CZ (2003) Molecular mechanisms regulating persistent Mycobacterium tuberculosis infection. Microbes Infect 5(2):159–167. doi:10.1016/s1286-4579(02)00083-7

    Article  Google Scholar 

  • Vergne I, Chua J, Singh SB, Deretic V (2004) Cell biology of Mycobacterium tuberculosis phagosome. Annu Rev Cell Dev Biol 20:367–394. doi:10.1146/annurev.cellbio.20.010403.114015

    Article  CAS  Google Scholar 

  • WHO (2010) Global Tuberculosis Control. Geneva

  • Wijagkanalan W, Kawakami S, Takenaga M, Igarashi R, Yamashita F, Hashida M (2008) Efficient targeting to alveolar macrophages by intratracheal administration of mannosylated liposomes in rats. J Controlled Release 125(2):121–130

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work was funded by the National Basic Research Programs of China (973 program, No: 2009CB930300 and 2012CB724002) and supported by the State Key Program of the National Natural Science of China (No: 81130060). The authors would like to thank W.R. Webb, ISTM Guy Hilton Research Centre, Keele University Medical School, for editorial assistance.

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The authors report no conflicts of interest.

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Authors and Affiliations

  1. Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17. Section 3 Southern Renmin Road, Chengdu, 610041, People’s Republic of China

    Junlan Chuan, Likai Yang, Xun Sun, Tao Gong & Zhirong Zhang

  2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, People’s Republic of China

    Yanzhen Li & Tao Gong

  3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China

    Qiang Zhang

  4. Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China

    Junlan Chuan

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  1. Junlan Chuan
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  2. Yanzhen Li
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  3. Likai Yang
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  4. Xun Sun
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  5. Qiang Zhang
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  6. Tao Gong
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  7. Zhirong Zhang
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Correspondence to Tao Gong or Zhirong Zhang.

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Chuan, J., Li, Y., Yang, L. et al. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles. J Nanopart Res 15, 1634 (2013). https://doi.org/10.1007/s11051-013-1634-1

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  • DOI: https://doi.org/10.1007/s11051-013-1634-1

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