Advertisement

Charge Modification of Pharmaceutical Nanocarriers: Biological Implications

  • N. Nafee
  • M. Schneider
  • C. -M. Lehr
Part of the Fundamental Biomedical Technologies book series (FBMT, volume 4)

Multifunctional particles may be necessary to target specific locations and overcome different barriers hampering the delivery of drugs using nanoparticulate matter (Fenart et al. 1999; Kreuter 2004; Lockman et al. 2004). The interaction taking place is based on several properties that are essential for the relation between particle and biological system. For instance, the multifunctional particles will allow to target a certain tissue, deliver an active component, and provide a marker to observe the successful delivery (McNeil 2005).

In this chapter we will focus on the charge as one of the most basic and crucial properties influencing the environmental interaction of nanoparticulate matter. The surface charge of the nanoscale particles is a standard parameter to be characterized and reported. This is attributed to the stability of the suspension, which is achieved by electrostatic repulsion or, less often, by sterical hindrance. Charge is mainly used for complexation. Especially, this holds for the intracellular delivery of genetic material (RNA, DNA, and oligonucleotides), which is typically negatively charged and therefore requires a positively charged carrier (Elouahabi and Ruysschaert 2005).

Keywords

Gene Delivery Silica Nanoparticles Cationic Lipid PLGA Nanoparticles Gene Delivery System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akiyoshi, K., Deguchi, S., Moriguchi, N., Yamaguchi, S. and Sunamoto, J. 1993. Self-aggregates of hydrophobized polysaccharides in water. Formation and characteristics of nanoparticles. Macromolecules 26:3062–3068.ADSCrossRefGoogle Scholar
  2. Amidi, M., Romeijn, S. G., Borchard, G., Junginger, H. E., Hennink, W. E. and Jiskoot, W. 2006. Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. Journal of Controlled Release 111:107–116.PubMedCrossRefGoogle Scholar
  3. Amidi, M., Romeijn, S. G., Verhoef, J. C., Junginger, H. E., Bungener, L., Huckriede, A., Crommelin, D. J. A. and Jiskoot, W. 2007. N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: Biological properties and immunogenicity in a mouse model. Vaccine 25:144–153.PubMedCrossRefGoogle Scholar
  4. Arruebo, M., Fernández-Pacheco, R., Ibarra, M. R. and Santamaría, J. 2007. Magnetic nanoparticles for drug delivery. Nano Today 2:22–32.CrossRefGoogle Scholar
  5. Baars, M. W. P. L., Kleppinger, R., Koch, M. H. J., Yeu, S.-L. and Meijer, E. W. 2000. The localization of guests in water-soluble oligoethyleneoxy-modified poly(propylene imine) dendrimers. Angewandte Chemie International Edition 39:1285–1288.CrossRefGoogle Scholar
  6. Baczynska, D., Widerak, K., Ugorski, M. and Langner, M. 2001. Surface charge and the association of liposomes with colon carcinoma cells. Zeitschrift fur Naturforschung C: A Journal of Biosciences 56:872–877.Google Scholar
  7. Barbé, C., Bartlett, J., Kong, L., Finnie, K., Lin, H. Q., Larkin, M., Calleja, S., Bush, A. and Calleja, G. 2004. Silica particles: A novel drug-delivery system. Advanced Materials 16:1959–1966.CrossRefGoogle Scholar
  8. Bhadra, D., Bhadra, S., Jain, S. and Jain, N. K. 2003. A PEGylated dendritic nanoparticulate carrier of fluorouracil. International Journal of Pharmaceutics 257:111–124.PubMedCrossRefGoogle Scholar
  9. Bhadra, D., Yadav, A. K., Bhadra, S. and Jain, N. K. 2005. Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting. International Journal of Pharmaceutics 295:221–233.PubMedCrossRefGoogle Scholar
  10. Bharali, D. J., Klejbor, I., Stachowiak, E. K., Dutta, P., Roy, I., Kaur, N., Bergey, E. J., Prasad, P. N. and Stachowiak, M. K. 2005. Organically modified silica nanoparticles: A nonviral vector for in vivo gene delivery and expression in the brain. Proceedings of the National Academy of Sciences of the United States of America 102:11539–11544.PubMedADSCrossRefGoogle Scholar
  11. Bivas-Benita, M., Romeijn, S., Junginger, H. E. and Borchard, G. 2004. PLGA-PEI nanoparticles for gene delivery to pulmonary epithelium. European Journal of Pharmaceutics and Biopharmaceutics 58:1–6.PubMedCrossRefGoogle Scholar
  12. Blau, S., Jubeh, T. T., Haupt, S. M. and Rubinstein, A. 2000. Drug targeting by surface cationization. Critical Reviews in Therapeutic Drug Carrier Systems 17:425–465.PubMedGoogle Scholar
  13. Borges, O., Borchard, G., Verhoef, J. C., de Sousa, A. and Junginger, H. E. 2005. Preparation of coated nanoparticles for a new mucosal vaccine delivery system. International Journal of Pharmaceutics 299:155–166.PubMedCrossRefGoogle Scholar
  14. Borm, P. J. A., Robbins, D., Haubold, S., Kuhlbusch, T., Fissan, H., Donaldson, K., Schins, R., Stone, V., Kreyling, W., Lademann, J., Krutmann, J., Warheit, D. B. and Oberdorster, E. 2006. The potential risks of nanomaterials: A review carried out for ECETOC. Particle and Fibre Toxicology 3:.Google Scholar
  15. Borowik, T., Widerak, K., Ugorski, M. and Langner, M. 2005. Combined effect of surface electrostatic charge and poly(ethyl glycol) on the association of liposomes with colon carcinoma cells. Journal of Liposome Research 15:199–213.PubMedCrossRefGoogle Scholar
  16. Bosman, A. W., Janssen, H. M. and Meijer, E. W. 1999. About dendrimers: Structure, physical properties, and applications. Chemical Reviews 99:1665–1688.PubMedCrossRefGoogle Scholar
  17. Boussif, O., Lezoualc’h, F., Zanta, M. A., Mergny, M. D., Scherman, D., Demeneix, B. and Behr, J. P. 1995. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proceedings of the National Academy of Sciences of the United States of America 92:7297–7301.PubMedADSCrossRefGoogle Scholar
  18. Brewster, L. P., Brey, E. M. and Greisler, H. P. 2006. Cardiovascular gene delivery: The good road is awaiting. Advanced Drug Delivery Reviews—Gene Delivery for Tissue Engineering 58:604–629.CrossRefGoogle Scholar
  19. Brunner, T. J., Wick, P., Manser, P., Spohn, P., Grass, R. N., Limbach, L. K., Bruinink, A. and Stark, W. J. 2006. In vitro cytotoxicity of oxide nanoparticles: Comparison to asbestos, silica, and the effect of particle solubility. Environmental Science and Technology 40:4374–4381.PubMedCrossRefGoogle Scholar
  20. Chanana, M., Gliozzi, A., Diaspro, A., Chodnevskaja, I., Huewel, S., Moskalenko, V., Ulrichs, K., Galla, H. J. and Krol, S. 2005. Interaction of polyelectrolytes and their composites with living cells. Nano Letters 5:2605–2612.PubMedADSCrossRefGoogle Scholar
  21. Chang, J. S., Chang, K. L. B., Hwang, D. F. and Kong, Z. L. 2007. In vitro cytotoxicity of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environmental Science and Technology 41:2064–2068.PubMedCrossRefGoogle Scholar
  22. Chen, F., Zhang, Z. R. and Huang, Y. 2007. Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. International Journal of Pharmaceutics 336:166–173.PubMedCrossRefGoogle Scholar
  23. Chen, M. and Von Mikecz, A. 2005. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Experimental Cell Research 305:51–62.PubMedCrossRefGoogle Scholar
  24. Cherng, J. Y., Van De Wetering, P., Talsma, H., Crommelin, D. J. A. and Hennink, W. E. 1996. Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino) ethyl methacrylate)-plasmid nanoparticles. Pharmaceutical Research 13:1038–1042.PubMedCrossRefGoogle Scholar
  25. Chiu, G. N. C., Bally, M. B. and Mayer, L. D. 2001. Selective protein interactions with phosphatidylserine containing liposomes alter the steric stabilization properties of poly(ethylene glycol). Biochimica et Biophysica Acta–Biomembranes 1510:56–69.CrossRefGoogle Scholar
  26. Chiu, G. N. C., Bally, M. B. and Mayer, L. D. 2002. Effects of phosphatidylserine on membrane incorporation and surface protection properties of exchangeable poly(ethylene glycol)-conjugated lipids. Biochimica et Biophysica Acta–Biomembranes 1560:37–50.CrossRefGoogle Scholar
  27. Choi, J. S., Lee, E. J., Choi, Y. H., Jeong, Y. J. and Park, J. S. 1999. Poly(ethylene glycol)-block-poly(L-lysine) dendrimer: Novel linear polymer/dendrimer block copolymer forming a spherical water-soluble polyionic complex with DNA. Bioconjugational Chemistry 10:62–65.CrossRefGoogle Scholar
  28. Choi, J. S., Joo, D. K., Kim, C. H., Kim, K. and Park, J. S. 2000. Synthesis of a barbell-like triblock copolymer, poly(L-lysine) dendrimer-block-poly(ethylene glycol)-block-poly(L-lysine) dendrimer, and its self-assembly with plasmid DNA. Journal of American Chemical Society 122:474–480.CrossRefGoogle Scholar
  29. Choi, Y. H., Liu, F., Kim, J.-S., Choi, Y. K., Jong Sang, P. and Kim, S. W. 1998. Polyethylene glycol-grafted poly-L-lysine as polymeric gene carrier. Journal of Controlled Release 54:39–48.PubMedCrossRefGoogle Scholar
  30. Chung, T. H., Wu, S. H., Yao, M., Lu, C. W., Lin, Y. S., Hung, Y., Mou, C. Y., Chen, Y. C. and Huang, D. M. 2007. The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3–L1 cells and human mesenchymal stem cells. Biomaterials 28:2959–2966.PubMedCrossRefGoogle Scholar
  31. Chung, T.-W., Liu, D.-Z., Hsieh, J.-H., Fan, X.-C., Yang, J.-D. and Chen, J.-H. 2006. Characterizing poly(C-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for doxorubicin (DOX) delivery: Effects of crosslinked of amine groups. Journal of Nanoscience and Nanotechnology 6:2902–2911.PubMedCrossRefGoogle Scholar
  32. Cuna, M., Alonso-Sande, M., Remunan-Lopez, C., Pivel, J. P., Alonso-Lebrero, J. L. and Alonso, M. J. 2006. Development of phosphorylated glucomannan-coated chitosan nanoparticles as nanocarriers for protein delivery. Journal of Nanoscience and Nanotechnology 6:2887–2895.PubMedCrossRefGoogle Scholar
  33. Dailey, L. A., Schmehl, T., Gessler, T., Wittmar, M., Grimminger, F., Seeger, W. and Kissel, T. 2003. Nebulization of biodegradable nanoparticles: Impact of nebulizer technology and nanoparticle characteristics on aerosol features. Journal of Controlled Release 86:131–144.PubMedCrossRefGoogle Scholar
  34. Dailey, L. A., Jekel, N., Fink, L., Gessler, T., Schmehl, T., Wittmar, M., Kissel, T. and Seeger, W. 2006. Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung. Toxicology and Applied Pharmacology 215:100–108.PubMedCrossRefGoogle Scholar
  35. Dalluge, R., Haberland, A., Zaitsev, S., Schneider, M., Zastrow, H., Sukhorukov, G. and Bottger, M. 2002. Characterization of structure and mechanism of transfection-active peptide-DNA complexes. Biochimica et Biophysica Acta (BBA)–Gene Structure and Expression 1576:45–52.CrossRefGoogle Scholar
  36. Dang, J. M. and Leong, K. W. 2006. Natural polymers for gene delivery and tissue engineering. Advanced Drug Delivery Reviews Gene Delivery for Tissue Engineering 58:487–499.CrossRefGoogle Scholar
  37. Dellian, M., Yuan, F., Trubetskoy, V. S., Torchilin, V. P. and Jain, R. K. 2000. Vascular permeability in a human tumour xenograft: Molecular charge dependence. British Journal of Cancer 82:1513–1518.PubMedCrossRefGoogle Scholar
  38. Dobson, J. 2006. Magnetic nanoparticles for drug delivery. Drug Development Research 67:55–60.CrossRefGoogle Scholar
  39. Dodane, V., Amin Khan, M. and Merwin, J. R. 1999. Effect of chitosan on epithelial permeability and structure. International Journal of Pharmaceutics 182:21–32.PubMedCrossRefGoogle Scholar
  40. Dubruel, P., Christiaens, B., Rosseneu, M., Vandekerckhove, J., Grooten, J., Goossens, V. and Schacht, E. 2004. Buffering properties of cationic polymethacrylates are not the only key to successful gene delivery. Biomacromolecules 5:379–388.PubMedCrossRefGoogle Scholar
  41. Dufes, C., Uchegbu, I. F. and Schatzlein, A. G. 2005. Dendrimers in gene delivery. Advanced Drug Delivery Reviews 57:2177–2202.PubMedCrossRefGoogle Scholar
  42. Duguid, J. G., Li, C., Shi, M., Logan, M. J., Alila, H., Rolland, A., Tomlinson, E., Sparrow, J. T. and Smith, L. C. 1998. A physicochemical approach for predicting the effectiveness of peptide-based gene delivery systems for use in plasmid-based gene therapy. Biophysical Journal 74:2802–2814.PubMedADSCrossRefGoogle Scholar
  43. El-Sayed, M., Rhodes, C. A., Ginski, M. and Ghandehari, H. 2003. Transport mechanism(s) of poly(amidoamine) dendrimers across Caco-2 cell monolayers. International Journal of Pharmaceutics 265:151–157.PubMedCrossRefGoogle Scholar
  44. El-Shabouri, M. H. 2002. Positively charged nanoparticles for improving the oral bioavailability of cyclosporin-A. International Journal of Pharmaceutics 249:101–108.PubMedCrossRefGoogle Scholar
  45. El Ouahabi, A., Thiry, M., Pector, V., Fuks, R., Ruysschaert, J. M. and Vandenbranden, M. 1997. The role of endosome destabilizing activity in the gene transfer process mediated by cationic lipids. FEBS Letters 414:187–192.PubMedCrossRefGoogle Scholar
  46. Elouahabi, A. and Ruysschaert, J. M. 2005. Formation and intracellular trafficking of lipoplexes and polyplexes. Molecular Therapy 11:336–347.PubMedCrossRefGoogle Scholar
  47. Erbacher, P., Zou, S., Bettinger, T., Steffan, A. M. and Remy, J. S. 1998. Chitosan-based vector/DNA complexes for gene delivery: Biophysical characteristics and transfection ability. Pharmaceutical Research 15:1332–1339.PubMedCrossRefGoogle Scholar
  48. Fahmy, T. M., Fong, P. M., Goyal, A. and Saltzman, W. M. 2005. Targeted for drug delivery. Materials Today 8:18–26.CrossRefGoogle Scholar
  49. Felberbaum-Corti, M., Van Der Goot, F. G. and Gruenberg, J. 2003. Sliding doors: Clathrin-coated pits or caveolae? Nature Cell Biology 5:382–384.PubMedCrossRefGoogle Scholar
  50. Felgner, J. H., Kumar, R., Sridhar, C. N., Wheeler, C. J., Tsai, Y. J., Border, R., Ramsey, P., Martin, M. and Felgner, P. L. 1994. Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. Journal of Biological Chemistry 269:2550–2561.PubMedGoogle Scholar
  51. Felgner, P. L. 1999. Progress in gene delivery research and development. In non-viral vectors for gene therapy, L. Huang, M. C. Hung, and E. Wagner (eds.). pp. 26–38. San Diego: Academic Press.Google Scholar
  52. Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M. and Danielsen, M. 1987. Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure. Proceedings of the National Academy of Sciences of the United States of America 84:7413–7417.PubMedADSCrossRefGoogle Scholar
  53. Fenart, L., Casanova, A., Dehouck, B., Duhem, C., Slupek, S., Cecchelli, R. and Betbeder, D. 1999. Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. Journal of Pharmacology and Experimental Therapeutics 291:1017–1022.PubMedGoogle Scholar
  54. Ferrari, M. 2005. Cancer nanotechnology: Opportunities and challenges. Nature Reviews Cancer 5:161–171.PubMedCrossRefGoogle Scholar
  55. Funhoff, A. M., van Nostrum, C. F., Koning, G. A., Schuurmans-Nieuwenbroek, N. M. E., Crommelin, D. J. A. and Hennink, W. E. 2004. Endosomal escape of polymeric gene delivery complexes is not always enhanced by polymers buffering at low pH. Biomacromolecules 5:32–39.PubMedCrossRefGoogle Scholar
  56. Gao, S., Chen, J., Xu, X., Ding, Z., Yang, Y.-H., Hua, Z. and Zhang, J. 2003. Galactosylated low molecular weight chitosan as DNA carrier for hepatocyte-targeting. International Journal of Pharmaceutics 255:57–68.PubMedCrossRefGoogle Scholar
  57. Gao, S., Chen, J., Dong, L., Ding, Z., Yang, Y.-H. and Zhang, J. 2005. Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector. European Journal of Pharmaceutics and Biopharmaceutics 60:327–334.PubMedCrossRefGoogle Scholar
  58. Garnett, M. C. 1999. Gene-delivery systems using cationic polymers. Critical Reviews in Therapeutic Drug Carrier Systems 16:147–207.PubMedGoogle Scholar
  59. Godbey, W. T., Wu, K. K., Hirasaki, G. J. and Mikos, A. G. 1999. Improved packing of poly(ethylenimine)/DNA complexes increases transfection efficiency. Gene Therapy 6:1380–1388.PubMedCrossRefGoogle Scholar
  60. Goodman, C. M., McCusker, C. D., Yilmaz, T. and Rotello, V. M. 2004. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjugate Chemistry 15:897–900.PubMedCrossRefGoogle Scholar
  61. Gupta, U., Agashe, H. B., Asthana, A. and Jain, N. K. 2006. A review of in vitro–in vivo investigations on dendrimers: The novel nanoscopic drug carriers. Nanomedicine: Nanotechnology, Biology and Medicine 2:66–73.Google Scholar
  62. Haas, J., Ravi Kumar, M., Borchard, G., Bakowsky, U. and Lehr, C.-M. 2005. Preparation and characterization of chitosan and trimethyl-chitosan-modified poly-(H-caprolactone) nanoparticles as DNA carriers. AAPS PharmSciTech 6:E22–E30.PubMedCrossRefGoogle Scholar
  63. Hafez, I. M., Ansell, S. and Cullis, P. R. 2000. Tunable pH-sensitive liposomes composed of mixtures of cationic and anionic lipids. Biophysical Journal 79:1438–1446.PubMedADSCrossRefGoogle Scholar
  64. Han, S.-o., Mahato, R. I. and Kim, S. W. 2001. Water-soluble lipopolymer for gene delivery. Bioconjugate Chemistry 12:337–345.CrossRefGoogle Scholar
  65. Harada, A., Togawa, H. and Kataoka, K. 2001. Physicochemical properties and nuclease resistance of antisense-oligodeoxynucleotides entrapped in the core of polyion complex micelles composed of poly(ethylene glycol)–poly(L-lysine) block copolymers. European Journal of Pharmaceutical Sciences 13:35–42.PubMedCrossRefGoogle Scholar
  66. Hardman, R. 2006. A toxicologic review of quantum dots: Toxicity depends on physicochemical and environmental factors. Environmental Health Perspectives 114:165–172.PubMedCrossRefGoogle Scholar
  67. Hariharan, S., Bhardwaj, V., Bala, I., Sitterberg, J., Bakowsky, U. and Ravi Kumar, M. N. V. 2006. Design of estradiol loaded PLGA nanoparticulate formulations: A potential oral delivery system for hormone therapy. Pharmaceutical Research 23:184–195.PubMedCrossRefGoogle Scholar
  68. Hashida, M., Nishikawa, M., Yamashita, F. and Takakura, Y. 2001. Cell-specific delivery of genes with glycosylated carriers. Advanced Drug Delivery Reviews 52:187–196.PubMedCrossRefGoogle Scholar
  69. He, X., Duan, J., Wang, K., Tan, W., Lin, X. and He, C. 2004. A novel fluorescent label based on organic dye-doped silica nanoparticles for HepG liver cancer cell recognition. Journal of Nanoscience and Nanotechnology 4:585–589.PubMedCrossRefGoogle Scholar
  70. He, X. X., Wang, K., Tan, W., Liu, B., Lin, X., He, C., Li, D., Huang, S. and Li, J. 2003. Bioconjugated nanoparticles for DNA protection from cleavage. Journal of the American Chemical Society 125:7168–7169.PubMedCrossRefGoogle Scholar
  71. Hench, L. L. and Wilson, J. 1986. Biocompatibility of silicates for medical use. In Silicon Biochemistry, D. Evered and M. O’Connor (eds.). pp. 231–246. Chichester: Wiley.Google Scholar
  72. Hong, S., Leroueil, P. R., Majoros, I. J., Orr, B. G., Baker Jr, J. R. and Banaszak Holl, M. M. 2007. The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chemistry and Biology 14:107–115.PubMedCrossRefGoogle Scholar
  73. Hosseinkhani, H., Aoyama, T., Ogawa, O. and Tabata, Y. 2002. Liver targeting of plasmid DNA by pullulan conjugation based on metal coordination. Journal of Controlled Release 83:287–302.PubMedCrossRefGoogle Scholar
  74. Huang, L. and Viroonchatapan, E. 1999. Introduction. In Non-Viral Vectors for Gene Therapy, L. Huang, M. C. Hung, and E. Wagner (eds.). pp. 3–22. San Diego: Academic Press.CrossRefGoogle Scholar
  75. Huang, M., Khor, E. and Lim, L.-Y. 2004. Uptake and cytotoxicity of chitosan molecules and nanparticles: Effects of molecular weight and degree of deacetylation. Pharmaceutical Research 21:344–353.PubMedCrossRefGoogle Scholar
  76. Hwa Kim, S., Hoon Jeong, J., Chul Cho, K., Wan Kim, S. and Gwan Park, T. 2005. Target-specific gene silencing by siRNA plasmid DNA complexed with folate-modified poly(ethylenimine). Journal of Controlled Release 104:223–232.PubMedCrossRefGoogle Scholar
  77. Illum, L. 2007. Nanoparticulate systems for nasal delivery of drugs: A real improvement over simple systems? Journal of Pharmaceutical Sciences 96:473–483.PubMedCrossRefGoogle Scholar
  78. Issa, M. M., Koping-Hoggard, M. and Artursson, P. 2005. Chitosan and the mucosal delivery of biotechnology drugs. Drug Discovery Today: Technologies 2:1–6.CrossRefGoogle Scholar
  79. Ito, A., Shinkai, M., Honda, H. and Kobayashi, T. 2005. Medical application of functionalized magnetic nanoparticles. Journal of Bioscience and Bioengineering 100:1–11.PubMedCrossRefGoogle Scholar
  80. Jain, T. K., Morales, M. A., Sahoo, S. K., Leslie-Pelecky, D. L. and Labhasetwar, V. 2005. Iron oxide nanoparticles for sustained delivery of anticancer agents. Molecular Pharmaceutics 2:194–205.PubMedCrossRefGoogle Scholar
  81. Janes, K., Calvo, P. and Alonso, M. 2001. Polysaccharide colloidal particles as delivery systems for macromolecules. Advanced Drug Delivery 47:83–97.CrossRefGoogle Scholar
  82. Jevprasesphant, R., Penny, J., Attwood, D. and D’Emanuele, A. 2004. Transport of dendrimer nanocarriers through epithelial cells via the transcellular route. Journal of Controlled Release 97:259–267.PubMedCrossRefGoogle Scholar
  83. Jo, J.-i., Yamamoto, M., Matsumoto, K., Nakamura, T. and Tabata, Y. 2006. Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression. Journal of Nanoscience and Nanotechnology 6:2853–2859.PubMedCrossRefGoogle Scholar
  84. Juliano, R. L. and Stamp, D. 1975. The effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs. Biochemical and Biophysical Research Communications 63:651–658.PubMedCrossRefGoogle Scholar
  85. Jung, T., Kamm, W., Breitenbach, A., Hungerer, K.-D., Hundt, E. and Kissel, T. 2001. Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): Evaluation of antibody response after oral and nasal application in mice. Pharmaceutical Research 18:352–360.PubMedCrossRefGoogle Scholar
  86. Kaneda, Y. and Tabata, Y. 2006. Non-viral vectors for cancer therapy. Cancer Science 97:348–354.PubMedCrossRefGoogle Scholar
  87. Kaul, G. and Amiji, M. 2005. Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin nanoparticles: In vitro and in vivo studies. Pharmaceutical Research 22:951–961.PubMedCrossRefGoogle Scholar
  88. Kawakami, H., Hiraka, K., Tamai, M., Horiuchi, A., Ogata, A., Hatsugai, T., Yamaguchi, A., Oyaizu, K. and Yuasa, M. 2007. pH-Sensitive liposome retaining Fe-porphyrin as SOD mimic for novel anticancer drug delivery system. Polymers for Advanced Technologies 18:82–87.CrossRefGoogle Scholar
  89. Kean, T., Roth, S. and Thanou, M. 2005. Trimethylated chitosans as non-viral gene delivery vectors: Cytotoxicity and transfection efficiency. Journal of Controlled Release 103:643–653.PubMedCrossRefGoogle Scholar
  90. Khalil, I. A., Kogure, K., Futaki, S., Hama, S., Akita, H., Ueno, M., Kishida, H., Kudoh, M., Mishina, Y., Kataoka, K., Yamada, M. and Harashima, H. 2007. Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery. Gene Therapy 14:682–689.PubMedCrossRefGoogle Scholar
  91. Kim, I.-S., Lee, S.-K., Park, Y.-M., Lee, Y.-B., Shin, S.-C., Lee, K. C. and Oh, I.-J. 2005. Physicochemical characterization of poly(L-lactic acid) and poly(D, L-lactide-co-glycolide) nanoparticles with polyethylenimine as gene delivery carrier. International Journal of Pharmaceutics 298:255–262.PubMedCrossRefGoogle Scholar
  92. Kim, J. S., Yoon, T. J., Yu, K. N., Kim, B. G., Park, S. J., Kim, H. W., Lee, K. H., Park, S. B., Lee, J. K. and Cho, M. H. 2006a. Toxicity and tissue distribution of magnetic nanoparticles in mice. Toxicological Sciences 89:338–347.PubMedCrossRefGoogle Scholar
  93. Kim, T. H., Nah, J. W., Cho, M. H., Park, T. G. and Cho, N. S. 2006b. Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles. Journal of Nanoscience and Nanotechnology 6:2796–2803.PubMedCrossRefGoogle Scholar
  94. Kim, T. H., Park, I. K., Nah, J. W., Choi, Y. J. and Cho, C. S. 2004. Galactosylated chitosan/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier. Biomaterials 25:3783–3792.PubMedCrossRefGoogle Scholar
  95. Klein, C. P. A. T., Li, P., De Blieck-Hogervorst, J. M. A. and De Groot, K. 1995. Effect of sintering temperature on silica gels and their bone bonding ability. Biomaterials 16:715–719.PubMedCrossRefGoogle Scholar
  96. Klibanov, A. L., Torchilin, V. P. and Zalipsky, S. 2003. Long-circulating sterically protected liposomes. In Liposomes, V. P. Torchilin and V. Weissig (eds.). 231 pp. Oxford, UK: Oxford University Press.Google Scholar
  97. Kneuer, C., Sameti, M., Bakowsky, U., Schiestel, T., Schirra, H., Schmidt, H. and Lehr, C. M. 2000a. A nonviral DNA delivery system based on surface modified silica-nanoparticles can efficiently transfect cells in vitro. Bioconjugate Chemistry 11:926–932.PubMedCrossRefGoogle Scholar
  98. Kneuer, C., Sameti, M., Haltner, E. G., Schiestel, T., Schirra, H., Schmidt, H. and Lehr, C. M. 2000b. Silica nanoparticles modified with aminosilanes as carriers for plasmid DNA. International Journal of Pharmaceutics 196:257–261.PubMedCrossRefGoogle Scholar
  99. Kneuer, G., Ehrhardt, C., Bakowsky, H., Kumar, M. N. V. R., Oberle, V., Lehr, C. M., Hoekstra, D. and Bakowsky, U. 2006. The influence of physicochemical parameters on the efficacy of non-viral DNA transfection complexes: A comparative study. Journal of Nanoscience and Nanotechnology 6:2776–2782.PubMedCrossRefGoogle Scholar
  100. Koch, A. M., Reynolds, F., Merkle, H. P., Weissleder, R. and Josephson, L. 2005. Transport of surface-modified nanoparticles through cell monolayers. ChemBioChem 6:337–345.PubMedCrossRefGoogle Scholar
  101. Kommareddy, S. and Amiji, M. 2007. Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery. Nanomedicine: Nanotechnology, Biology and Medicine 3:32–42.Google Scholar
  102. Kreuter, J. 2004. Influence of the surface properties on nanoparticle-mediated transport of drugs to the brain. Journal of Nanoscience and Nanotechnology 4:484–488.PubMedCrossRefGoogle Scholar
  103. Kunath, K., von Harpe, A., Fischer, D. and Kissel, T. 2003. Galactose-PEI-DNA complexes for targeted gene delivery: Degree of substitution affects complex size and transfection efficiency. Journal of Controlled Release 88:159–172.PubMedCrossRefGoogle Scholar
  104. Kwoh, D. Y., Coffin, C. C., Lollo, C. P., Jovenal, J., Banaszczyk, M. G., Mullen, P., Phillips, A., Amini, A., Fabrycki, J., Bartholomew, R. M., Brostoff, S. W. and Carlo, D. J. 1999. Stabilization of poly-L-lysine/DNA polyplexes for in vivo gene delivery to the liver. Biochimica et Biophysica Acta (BBA)–Gene Structure and Expression 1444:171–190.CrossRefGoogle Scholar
  105. Kwon, H. Y., Lee, J. Y., Choi, S. W., Jang, Y. and Kim, J. H. 2001. Preparation of PLGA nanoparticles containing estrogen by emulsification-diffusion method. Colloids and Surfaces A: Physicochemical and Engineering Aspects 182:123–130.CrossRefGoogle Scholar
  106. Lai, W., Ducheyne, P. and Garino, J. 1998. Removal pathway of silicon released from bioactive glass granules in vivo. In Bioceramics, R. Z. LeGeros and J. P. LeGeros (eds.). pp. 383–386. New York: World Scientific.Google Scholar
  107. Lai, W., Ducheyne, P., Garino, J. and Flaitz, C. M. 2000. Removal pathway of bioactive glass resorption products from the body. Materials Research Society Symposium–Proceedings 599:261–266.Google Scholar
  108. Lai, W., Garino, J., Flaitz, C. and Ducheyne, P. 2005. Excretion of resorption products from bioactive glass implanted in rabbit muscle. Journal of Biomedical Materials Research Part A 75:398–407.PubMedCrossRefGoogle Scholar
  109. Lampela, P., Soininen, P., Urtti, A., Mannisto, P. T. and Raasmaja, A. 2004. Synergism in gene delivery by small PEIs and three different nonviral vectors. International Journal of Pharmaceutics 270:175–184.PubMedCrossRefGoogle Scholar
  110. Lehr, C. M., Bouwstra, J. A., Tukker, J. J. and Junginger, H. E. 1990. Intestinal transit of bioadhesive microspheres in an in situ loop in the rat–A comparative study with copolymers and blends based on poly(acrylic acid). Journal of Controlled Release 13:51–62.CrossRefGoogle Scholar
  111. Levy, L., Sahoo, Y., Kim, K. S., Bergey, E. J. and Prasad, P. N. 2002. Nanochemistry: Synthesis and characterization of multifunctional nanoclinics for biological applications. Chemistry of Materials 14:3715–3721.CrossRefGoogle Scholar
  112. Li, P., Ohtsuki, C., Kokubo, T., Nakanishi, K., Soga, N. and De Groot, K. 1994. The role of hydrated silica, titania, and alumina in inducing apatite on implants. Journal of Biomedical Materials Research 28:7–15.PubMedCrossRefGoogle Scholar
  113. Li, S. and Huang, L. 2000. Nonviral gene therapy: Promises and challenges. Gene Therapy 7:31–34.PubMedCrossRefGoogle Scholar
  114. Liu, W. G., Yao, K. D. and Liu, Q. G. 2001. Formation of a DNA/N-dodecylated chitosan complex and salt-induced gene delivery. Journal of Applied Polymer Sciences 82:3391–3395.CrossRefGoogle Scholar
  115. Lockman, P. R., Koziara, J. M., Mumper, R. J. and Allen, D. 2004. Nanoparticle surface charges alter blood-brain barrier integrity and permeability. Journal of Drug Targeting 12:635–641.PubMedCrossRefGoogle Scholar
  116. Lu, H., Yi, G., Zhao, S., Chen, D., Guo, L. H. and Cheng, J. 2004. Synthesis and characterization of multi-functional nanoparticles possessing magnetic, up-conversion fluorescence and bio-affinity properties. Journal of Materials Chemistry 14:1336–1341.CrossRefGoogle Scholar
  117. Lu, Y., Yin, Y., Mayers, B. T. and Xia, Y. 2002. Modifying the surface properties of superparamagnetic iron oxide nanoparticles through a sol-gel approach. Nano Letters 2:183–186.ADSCrossRefGoogle Scholar
  118. Luo, D., Han, E., Belcheva, N. and Saltzman, W. M. 2004. A self-assembled, modular DNA delivery system mediated by silica nanoparticles. Journal of Controlled Release 95:333–341.PubMedCrossRefGoogle Scholar
  119. Lv, H., Zhang, S., Wang, B., Cui, S. and Yan, J. 2006. Toxicity of cationic lipids and cationic polymers in gene delivery. Journal of Controlled Release 114:100–109.PubMedCrossRefGoogle Scholar
  120. Maksimenko, A., Mandrouguine, V., Gottikh, M. B., Bertrand, J.-R., Majoral, J.-P. and Malvy, C. 2003. Optimisation of dendrimer-mediated gene transfer by anionic oligomers. Journal of Gene Medicine 5:61–71.PubMedCrossRefGoogle Scholar
  121. Malik, N., Wiwattanapatapee, R., Klopsch, R., Lorenz, K., Frey, H., Weener, J. W., Meijer, E. W., Paulus, W. and Duncan, R. 2000. Dendrimers: Relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. Journal of Controlled Release 65:133–148.PubMedCrossRefGoogle Scholar
  122. Mansouri, S., Lavigne, P., Corsi, K., Benderdour, M., Beaumont, E. and Fernandes, J. C. 2004. Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: Strategies to improve transfection efficacy. European Journal of Pharmaceutics and Biopharmaceutics 57:1–8.PubMedCrossRefGoogle Scholar
  123. Mao, S., Shuai, X., Unger, F., Wittmar, M., Xie, X. and Kissel, T. 2005. Synthesis, characterization and cytotoxicity of poly(ethylene glycol)-graft-trimethyl chitosan block copolymers. Biomaterials 26:6343–6356.PubMedCrossRefGoogle Scholar
  124. Meers, P. 2001. Enzyme-activated targeting of liposomes. Advanced Drug Delivery Reviews 53:265–272.PubMedCrossRefGoogle Scholar
  125. Messai, I., Munier, S., Ataman-Onal, Y., Verrier, B. and Delair, T. 2003. Elaboration of poly(ethyleneimine) coated poly(D,L-lactic acid) particles. Effect of ionic strength on the surface properties and DNA binding capabilities. Colloids and Surfaces B: Biointerfaces 32:293–305.CrossRefGoogle Scholar
  126. Milhem, O. M., Myles, C., McKeown, N. B., Attwood, D. and D’Emanuele, A. 2000. Polyamidoamine Starburst® dendrimers as solubility enhancers. International Journal of Pharmaceutics 197:239–241.PubMedCrossRefGoogle Scholar
  127. Milton Harris, J. and Chess, R. B. 2003. Effect of pegylation on pharmaceuticals. Nature Reviews Drug Discovery 2:214–221.PubMedCrossRefGoogle Scholar
  128. Mislick, K. A. and Baldeschwieler, J. D. 1996. Evidence for the role of proteoglycans in cation-mediated gene transfer. Proceedings of the National Academy of Sciences of the United States of America 93:12349–12354.PubMedADSCrossRefGoogle Scholar
  129. Munier, S., Messai, I., Delair, T., Verrier, B. and Ataman-Onal, Y. 2005. Cationic PLA nanoparticles for DNA delivery: Comparison of three surface polycations for DNA binding, protection and transfection properties. Colloids and Surfaces B: Biointerfaces 43:163–173.CrossRefGoogle Scholar
  130. Nafee, N., Taetz, S., Schneider, M., Schaefer, U. F. and Lehr, C. M. in press. Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: Effect of the formulation parameters on complexation and transfection of antisense oligonucleotides. Nanomedicine: Nanotechnology, Biology, and Medicine.Google Scholar
  131. Nel, A., Xia, T., Madler, L. and Li, N. 2006. Toxic potential of materials at the nanolevel. Science 311:622–627; DOI: 10.1126/science.1114397.PubMedADSCrossRefGoogle Scholar
  132. Nemmar, A., Vanbilloen, H., Hoylaerts, M. F., Hoet, P. H. M., Verbruggen, A. and Nemery, B. 2001. Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. American Journal of Respiratory and Critical Care Medicine 164:1665–1668.PubMedGoogle Scholar
  133. Ohya, Y., Cai, R., Nishizawa, H., Hara, K. and Ouchi, T. 1999. Preparation of PEG-grafted chitosan nano-particle for peptide drug carrier. Proceedings of the International Symposium on Controlled Release of Bioactive Materials 26:655–656.Google Scholar
  134. Oku, N., Yamazaki, Y., Matsuura, M., Sugiyama, M., Hasegawa, M. and Nango, M. 2001. A novel non-viral gene transfer system, polycation liposomes. Advanced Drug Delivery Reviews 52:209–218.PubMedCrossRefGoogle Scholar
  135. Osborne, M. P., Richardson, V. J., Jeyasingh, K. and Ryman, B. E. 1979. Radionuclide-labelled liposomes. A new lymph node imaging agent. International Journal of Nuclear Medicine and Biology 6:75–83.PubMedCrossRefGoogle Scholar
  136. Oster, C., Wittmar, M., Unger, F., Barbu-Tudoran, L., Schaper, A. and Kissel, T. 2004. Design of amine-modified graft polyesters for effective gene delivery using DNA-loaded nanoparticles. Pharmaceutical Research 21:927–931.PubMedCrossRefGoogle Scholar
  137. Oussoren, C. and Storm, G. 2001. Liposomes to target the lymphatics by subcutaneous administration. Advanced Drug Delivery Reviews 50:143–156.PubMedCrossRefGoogle Scholar
  138. Ow, H., Larson, D. R., Srivastava, M., Baird, B. A., Webb, W. W. and Wiesnert, U. 2005. Bright and stable core-shell fluorescent silica nanoparticles. Nano Letters 5:113–117.PubMedADSCrossRefGoogle Scholar
  139. Pang, S. W., Park, H. Y., Jang, Y. S., Kim, W. S. and Kim, J. H. 2002. Effects of charge density and particle size of poly(styrene/(dimethylamino) ethyl methacrylate) nanoparticle for gene delivery in 293 cells. Colloids and Surfaces B: Biointerfaces 26:213–222.CrossRefGoogle Scholar
  140. Panyam, J. and Labhasetwar, V. 2003. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews 55:329–347.PubMedCrossRefGoogle Scholar
  141. Park, T. G., Jeong, J. H. and Kim, S. W. 2006. Current status of polymeric gene delivery systems. Advanced Drug Delivery Reviews Gene Delivery for Tissue Engineering 58:467–486.CrossRefGoogle Scholar
  142. Patel, H. M., Boodle, K. M. and Vaughan-Jones, R. 1984. Assessment of the potential uses of liposomes for lymphoscintigraphy and lymphatic drug delivery. Failure of 99m-technetium marker to represent intact liposomes in lymph nodes. Biochimica et Biophysica Acta–General Subjects 801:76–86.CrossRefGoogle Scholar
  143. Peng, J., He, X., Wang, K., Tan, W., Li, H., Xing, X. and Wang, Y. 2006. An antisense oligonucleotide carrier based on amino silica nanoparticles for antisense inhibition of cancer cells. Nanomedicine: Nanotechnology, Biology, and Medicine 2:113–120.CrossRefGoogle Scholar
  144. Petersen, H., Fechner, P. M., Martin, A. L., Kunath, K., Stolnik, S., Roberts, C. J., Fischer, D., Davies, M. C. and Kissel, T. 2002. Polyethylenimine-graft-poly(ethylene glycol) copolymers: Influence of copolymer block structure on DNA complexation and biological activities as gene delivery system. Bioconjugate Chemistry 13:845–854.PubMedCrossRefGoogle Scholar
  145. Preece, J. A. 2007. Proton sponge. Nanoscale Chemistry Research Group at University of Birmingham. http://www.nanochem.bham.ac.uk/gene_delivery/protonsponge.htm.
  146. Qhobosheane, M., Santra, S., Zhang, P. and Tan, W. 2001. Biochemically functionalized silica nanoparticles. Analyst 126:1274–1278.PubMedADSCrossRefGoogle Scholar
  147. Ravi Kumar, M. N. V., Sameti, M., Mohapatra, S. S., Kong, X., Lockey, R. F., Bakowsky, U., Lindenblatt, G., Schmidt, H. and Lehr, C. M. 2004. Cationic silica nanoparticles as gene carriers: Synthesis, characterization and transfection efficiency in vitro and in vivo. Journal of Nanoscience and Nanotechnology 4:876–881.PubMedCrossRefGoogle Scholar
  148. Ribeiro, S., Hussain, N. and Florence, A. T. 2005. Release of DNA from dendriplexes encapsulated in PLGA nanoparticles. International Journal of Pharmaceutics (Selected contributions from the 5th European Workshop on Particulate Systems) 298:354–360.PubMedCrossRefGoogle Scholar
  149. Roy, I., Ohulchanskyy, T. Y., Bharali, D. J., Pudavar, H. E., Mistretta, R. A., Kaur, N. and Prasad, P. N. 2005. Optical tracking of organically modified silica nanoparticles as DNA carriers: A nonviral, nanomedicine approach for gene delivery. Proceedings of the National Academy of Sciences of the United States of America 102:279–284.PubMedADSCrossRefGoogle Scholar
  150. Roy, I., Ohulchanskyy, T. Y., Pudavar, H. E., Bergey, E. J., Oseroff, A. R., Morgan, J., Dougherty, T. J. and Prasad, P. N. 2003. Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drugs: A novel drug-carrier system for photodynamic therapy. Journal of the American Chemical Society 125:7860–7865.PubMedCrossRefGoogle Scholar
  151. Sakthivel, T., Istvan, T. and Alexander, T. F. 1998. Synthesis and physicochemical properties of lipophilic polyamide dendrimers. Pharmaceutical Research 15:776–782.PubMedCrossRefGoogle Scholar
  152. Sakurai, F., Inoue, R., Nishino, Y., Okuda, A., Matsumoto, O., Taga, T., Yamashita, F., Takakura, Y. and Hashida, M. 2000. Effect of DNA/liposome mixing ratio on the physicochemical characteristics, cellular uptake and intracellular trafficking of plasmid DNA/cationic liposome complexes and subsequent gene expression. Journal of Controlled Release 66:255–269.PubMedCrossRefGoogle Scholar
  153. Sano, A., Maeda, M., Nagahara, S., Ochiya, T., Honma, K., Itoh, H., Miyata, T. and Fujioka, K. 2003. Atelocollagen for protein and gene delivery. Advanced Drug Delivery Reviews 55:1651–1677.PubMedCrossRefGoogle Scholar
  154. Santra, S., Zhang, P., Wang, K., Tapec, R. and Tan, W. 2001. Conjugation of biomolecules with luminophore-doped silica nanoparticles for photostable biomarkers. Analytical Chemistry 73:4988–4993.PubMedCrossRefGoogle Scholar
  155. Schatzlein, A. G., Zinselmeyer, B. H., Elouzi, A., Dufes, C., Chim, Y. T. A., Roberts, C. J., Davies, M. C., Munro, A., Gray, A. I. and Uchegbu, I. F. 2005. Preferential liver gene expression with polypropylenimine dendrimers. Journal of Controlled Release 101:247–258.PubMedCrossRefGoogle Scholar
  156. Shah, D. S., Sakthivel, T., Toth, I., Florence, A. T. and Wilderspin, A. F. 2000. DNA transfection and transfected cell viability using amphipathic asymmetric dendrimers. International Journal of Pharmaceutics 208:41–48.PubMedCrossRefGoogle Scholar
  157. Shakweh, M., Besnard, M., Nicolas, V. and Fattal, E. 2005. Poly (lactide-co-glycolide) particles of different physicochemical properties and their uptake by Peyer’s patches in mice. European Journal of Pharmaceutics and Biopharmaceutics 61:1–13.PubMedCrossRefGoogle Scholar
  158. Shi, C., Zhu, Y., Ran, X., Wang, M., Su, Y. and Cheng, T. 2006. Therapeutic potential of chitosan and its derivatives in regenerative medicine. Journal of Surgical Research 133:185–192.PubMedCrossRefGoogle Scholar
  159. Shigeru, K., Shintaro, F., Makiya, N., Fumiyoshi, Y. and Mitsuru, H. 2000. In vivo gene delivery to the liver using novel galactosylated cationic liposomes. Pharmaceutical Research 17:306–313.CrossRefGoogle Scholar
  160. Simon, M., Wittmar, M., Kissel, T. and Linn, T. 2005. Insulin containing nanocomplexes formed by self-assembly from biodegradable amine-modified poly(vinyl alcohol)-graft-poly(L-lactide): Bioavailability and nasal tolerability in rats. Pharmaceutical Research 22:1879–1886.PubMedCrossRefGoogle Scholar
  161. Singh, M., Ugozzoli, M., Briones, M., Kazzaz, J., Soenawan, E. and O’Hagan, D. T. 2003. The effect of CTAB concentration in cationic PLG microparticles on DNA adsorption and in vivo performance. Pharmaceutical Research 20:247–251.PubMedCrossRefGoogle Scholar
  162. Spierings, G. A. C. M., Haisma, J. and Michielsen, T. M. 1995. Surface-related phenomena in the direct bonding of silicon and fused-silica wafer pairs. Philips Journal of Research 49:47–63.CrossRefGoogle Scholar
  163. Steimer, A., Haltner, E. and Lehr, C.-M. 2005. Cell culture models of the respiratory tract relevant to pulmonary drug delivery. Journal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung 18:137–182.Google Scholar
  164. Thanou, M., Florea, B. I., Geldof, M., Junginger, H. E. and Borchard, G. 2002. Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials 23:153–159.PubMedCrossRefGoogle Scholar
  165. Torchilin, V. P. 1998. Polymer-coated long-circulating microparticulate pharmaceuticals. Journal of Microencapsulation 15:1–19.PubMedCrossRefGoogle Scholar
  166. Torchilin, V. P. 2001. Structure and design of polymeric surfactant-based drug delivery systems. Journal of Controlled Release 73:137–172.PubMedCrossRefGoogle Scholar
  167. Torchilin, V. P. 2006. Multifunctional nanocarriers. Advanced Drug Delivery Reviews 58:1532–1555.PubMedCrossRefGoogle Scholar
  168. Torchilin, V. P., Weissig, V., Martin, F. J. and Heath, T. D. 2003. Surface modifications of liposomes. In Liposomes, V. P. Torchilin and V. Weissig (eds.). pp. 193–230. Oxford, UK: Oxford University Press.Google Scholar
  169. Trimaille, T., Pichot, C. and Delair, T. 2003. Surface functionalization of poly(D,L-lactic acid) nanoparticles with poly(ethylenimine) and plasmid DNA by the layer-by-layer approach. Colloids and Surfaces A: Physicochemical and Engineering Aspects 221:39–48.CrossRefGoogle Scholar
  170. Trubetskoy, V. S., Cannillo, J. A., Milshtein, A., Wolf, G. L. and Torchilin, V. P. 1995. Controlled delivery of Gd-containing liposomes to lymph nodes: Surface modification may enhance MRI contrast properties. Magnetic Resonance Imaging 13:31–37.PubMedCrossRefGoogle Scholar
  171. Uchegbu, I. F., Schätzlein, A. G., Tetley, L., Gray, A. I., Sludden, J., Siddique, S. and Mosha, E. 1998. Polymeric chitosan-based vesicles for drug delivery. Journal of Pharmacy and Pharmacology 50:453–458.PubMedGoogle Scholar
  172. Ulman, A. 1990. Self-assembled monolayers of alkyltrichlorosilanes: Building blocks for future organic materials. Advanced Materials 2:573–582.CrossRefGoogle Scholar
  173. Unger, F., Wittmar, M. and Kissel, T. 2007. Branched polyesters based on poly[vinyl-3-(dialkyla-mino) alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(D, L-lactide-co-glycolide): Effects of polymer structure on cytotoxicity. Biomaterials 28:1610–1619.PubMedCrossRefGoogle Scholar
  174. Vila, A., Sanchez, A., Tobio, M., Calvo, P. and Alonso, M. J. 2002. Design of biodegradable particles for protein delivery. Journal of Controlled Release 78:15–24.PubMedCrossRefGoogle Scholar
  175. Vila, A., Gill, H., McCallion, O. and Alonso, M. J. 2004. Transport of PLA–PEG particles across the nasal mucosa: Effect of particle size and PEG coating density. Journal of Controlled Release 98:231–244.PubMedCrossRefGoogle Scholar
  176. Vincent, L., Varet, J., Pille, J.-Y., Bompais, H., Opolon, P., Maksimenko, A., Malvy, C., Mirshahi, M., Lu, H., Vannier, J.-P., Soria, C. and Li, H. 2003. Efficacy of dendrimer-mediated angiostatin and TIMP-2 gene delivery on inhibition of tumor growth and angiogenesis: In vitro and in vivo studies. International Journal of Cancer 105:419–429.CrossRefGoogle Scholar
  177. Wall, D. A., Wilson, G. and Hubbard, A. L. 1980. The galactose-specific recognition system of mammalian liver: The route of ligand internalization in rat hepatocytes. Cell 21:79–93.PubMedCrossRefGoogle Scholar
  178. Wang, J., Lee, I. L., Lim, W. S., Chia, S. M., Yu, H., Leong, K. W. and Mao, H.-Q. 2004. Evaluation of collagen and methylated collagen as gene carriers. International Journal of Pharmaceutics 279:115–126.PubMedCrossRefGoogle Scholar
  179. Wang, L., Wang, K., Santra, S., Zhao, X., Hilliard, L. R., Smith, J. E., Wu, Y. and Tan, W. 2006. Watching silica nanoparticles glow in the biological world. Analytical Chemistry 78:646–654.CrossRefGoogle Scholar
  180. Watson, P., Jones, A. T. and Stephens, D. J. 2005. Intracellular trafficking pathways and drug delivery: Fluorescence imaging of living and fixed cells. Advanced Drug Delivery Reviews 57:43–61.PubMedCrossRefGoogle Scholar
  181. Weiss, B., Schneider, M., Muys, L., Taetz, S., Neumann, D., Schaefer, U. F. and Lehr, C. M. in press. Coupling of biotin-(poly(ethylene glycol)) amine to poly(D, L-lactide-co-glycolide) nanoparticles for versatile surface modification. Bioconjugate Chemistry.Google Scholar
  182. Westedt, U., Kalinowski, M., Wittmar, M., Merdan, T., Unger, F., Fuchs, J., Schaller, S., Bakowsky, U. and Kissel, T. 2007. Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment. Journal of Controlled Release 119:41–51.PubMedCrossRefGoogle Scholar
  183. Wiener, E., Brechbiel, M., Brothers, W. H., Magin, R. L., Gansow, O. A., Tomalia, D. A. and Lauterbur, P. C. 1994. Dendrimer-based metal chelates: A new class of magnetic resonance imaging contrast agents. 31:1–8.Google Scholar
  184. Wiwattanapatapee, R., Carreño-Gómez, B., Malik, N. and Duncan, R. 2000. Anionic PAMAM dendrimers rapidly cross adult rat intestine in vitro: A potential oral delivery system? Pharmaceutical Research 17:991–998.PubMedCrossRefGoogle Scholar
  185. Wu, G. Y. and Wu, C. H. 1987. Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. Journal of Biological Chemistry 262:4429–4432.PubMedGoogle Scholar
  186. Yessine, M. A., Lafleur, M., Meier, C., Petereit, H. U. and Leroux, J. C. 2003. Characterization of the membrane-destabilizing properties of different pH-sensitive methacrylic acid copolymers. Biochimica et Biophysica Acta–Biomembranes 1613:28–38.CrossRefGoogle Scholar
  187. Yessine, M. A. and Leroux, J. C. 2004. Membrane-destabilizing polyanions: Interaction with lipid bilayers and endosomal escape of biomacromolecules. Advanced Drug Delivery Reviews 56:999–1021.PubMedCrossRefGoogle Scholar
  188. Yuan, F., Dellian, M., Fukumura, D., Leunig, M., Berk, D. A., Torchilin, V. P. and Jain, R. K. 1995. Vascular permeability in a human tumor xenograft: Molecular size dependence and cutoff size. Cancer Research 55:3752–3756.PubMedGoogle Scholar
  189. Zhang, X. and Godbey, W. T. 2006. Viral vectors for gene delivery in tissue engineering. Advanced Drug Delivery Reviews Gene Delivery for Tissue Engineering 58:515–534.CrossRefGoogle Scholar
  190. Zhang, Z. and Feng, S.-S. 2006. The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials 27:4025–4033.PubMedMathSciNetCrossRefGoogle Scholar
  191. Zhao, X., Hilliard, L. R., Mechery, S. J., Wang, Y., Bagwe, R. P., Jin, S. and Tan, W. 2004. A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. Proceedings of the National Academy of Sciences of the United States of America 101:15027–15032.PubMedADSCrossRefGoogle Scholar
  192. Zhu, S. G., Xiang, J. J., Li, X. L., Shen, S. R., Lu, H. B., Zhou, J., Xiong, W., Zhang, B. C., Nie, X. M., Zhou, M., Tang, K. and Li, G. Y. 2004. Poly(L-lysine)-modified silica nanoparticles for the delivery of antisense oligonucleotides. Biotechnology and Applied Biochemistry 39:179–187.PubMedCrossRefGoogle Scholar
  193. Zhuravlev, L. T. 1987. Concentration of hydroxyl-groups on the surface of amorphous silicas. Langmuir 3:316–318.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • N. Nafee
    • 1
  • M. Schneider
    • 2
  • C. -M. Lehr
    • 2
  1. 1.Biopharmaceutics and Pharmaceutical TechnologySaarland UniversityGermany
  2. 2.Institute of BiopharmaceuticsSaarland UniversityGermany

Personalised recommendations