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BioMed Research International
Volume 2013 (2013), Article ID 382184, 20 pages
http://dx.doi.org/10.1155/2013/382184
Review Article

Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

1Herbal Medicinal Products Department, CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow 226015, India
2Centre of Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Mohali, Punjab 160062, India

Received 24 April 2013; Revised 14 August 2013; Accepted 25 August 2013

Academic Editor: Umesh Gupta

Copyright © 2013 Nidhi Mishra et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. Abe, T. Masuda, and R. Satodate, “Phagocytic activity of Kupffer cells in splenectomized rats,” Virchows Archiv A, vol. 413, no. 5, pp. 457–462, 1988. View at Scopus
  2. E. Wisse, F. Jacobs, B. Topal, P. Frederik, and B. De Geest, “The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer,” Gene Therapy, vol. 15, no. 17, pp. 1193–1199, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. J. A. Champion, A. Walker, and S. Mitragotri, “Role of particle size in phagocytosis of polymeric microspheres,” Pharmaceutical Research, vol. 25, no. 8, pp. 1815–1821, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. W. Jiang, B. Y. S. Kim, J. T. Rutka, and W. C. W. Chan, “Nanoparticle-mediated cellular response is size-dependent,” Nature Nanotechnology, vol. 3, no. 3, pp. 145–150, 2008. View at Publisher · View at Google Scholar
  5. X. Banquy, F. Suarez, A. Argaw et al., “Effect of mechanical properties of hydrogel nanoparticles on macrophage cell uptake,” Soft Matter, vol. 5, no. 20, pp. 3984–3991, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. J.-O. You and D. T. Auguste, “Nanocarrier cross-linking density and pH sensitivity regulate intracellular gene transfer,” Nano Letters, vol. 9, no. 12, pp. 4467–4473, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. C. He, Y. Hu, L. Yin, C. Tang, and C. Yin, “Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles,” Biomaterials, vol. 31, no. 13, pp. 3657–3666, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Funato, R. Yoda, and H. Kiwada, “Contribution of complement system on destabilization of liposomes composed of hydrogenated egg phosphatidylcholine in rat fresh plasma,” Biochimica et Biophysica Acta, vol. 1103, no. 2, pp. 198–204, 1992. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Nishikawa, H. Arai, and K. Inoue, “Scavenger receptor-mediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages,” Journal of Biological Chemistry, vol. 265, no. 9, pp. 5226–5231, 1990. View at Scopus
  10. P. J. Morgan, S. E. Harding, and K. Petrak, “Interactions of a model block copolymer drug delivery system with two serum proteins and myoglobin,” Biochemical Society Transactions, vol. 18, no. 5, pp. 1021–1022, 1990. View at Scopus
  11. P. Opanasopit, M. Nishikawa, and M. Hashida, “Factors affecting drug and gene delivery: effects of interaction with blood components,” Critical Reviews in Therapeutic Drug Carrier Systems, vol. 19, no. 3, pp. 191–233, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Boddy, L. Aarons, and K. Petrak, “Efficiency of drug targeting: steady-state considerations using a three-compartment model,” Pharmaceutical research, vol. 6, no. 5, pp. 367–372, 1989. View at Scopus
  13. K. Petrak and P. Goddard, “Transport of macromolecules across the capillary walls,” Advanced Drug Delivery Reviews, vol. 3, no. 2, pp. 191–214, 1989. View at Scopus
  14. K.-I. Ogawara, M. Yoshida, K. Higaki et al., “Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution,” Journal of Controlled Release, vol. 59, no. 1, pp. 15–22, 1999. View at Publisher · View at Google Scholar · View at Scopus
  15. T. M. Allen, C. Hansen, F. Martin, C. Redemann, and A. F. Yau-Young, “Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo,” Biochimica et Biophysica Acta, vol. 1066, no. 1, pp. 29–36, 1991. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Wu, M. H. Nantz, and M. A. Zern, “Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications,” Front Biosci, vol. 7, pp. d717–d725, 2002. View at Scopus
  17. P. C. N. Rensen, L. A. J. M. Sliedregt, M. Ferns et al., “Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and in vivo,” Journal of Biological Chemistry, vol. 276, no. 40, pp. 37577–37584, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. P. C. N. Rensen, M. C. M. Van Dijk, E. C. Havenaar, M. K. Bijsterbosch, J. K. Kruijt, and T. J. C. Van Berkel, “Selective liver targeting of antivirals by recombinant chylomicrons—a new therapeutic approach to hepatitis B,” Nature Medicine, vol. 1, no. 3, pp. 221–225, 1995. View at Scopus
  19. C. Wolfrum, S. Shi, K. N. Jayaprakash et al., “Mechanisms and optimization of in vivo delivery of lipophilic siRNAs,” Nature Biotechnology, vol. 25, no. 10, pp. 1149–1157, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Akinc, W. Querbes, S. De et al., “Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms,” Molecular Therapy, vol. 18, no. 7, pp. 1357–1364, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. M. K. Bijsterbosch, E. T. Rump, R. L. A. De Vrueh et al., “Modulation of plasma protein binding and in vivo liver cell uptake of phosphorothioate oligodeoxynucleotides by cholesterol conjugation,” Nucleic Acids Research, vol. 28, no. 14, pp. 2717–2725, 2000. View at Scopus
  22. K. M. Wasan, D. R. Brocks, S. D. Lee, K. Sachs-Barrable, and S. J. Thornton, “Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs: implications for drug discovery,” Nature Reviews Drug Discovery, vol. 7, no. 1, pp. 84–99, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. S. Kunjachan, S. Jose, C. A. Thomas, E. Joseph, F. Kiessling, and T. Lammers, “Physicochemical and biological aspects of macrophage-mediated drug targeting in anti-microbial therapy,” Fundamental and Clinical Pharmacology, vol. 26, no. 1, pp. 63–71, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Sato, K. Murase, J. Kato et al., “Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone,” Nature Biotechnology, vol. 26, no. 4, pp. 431–442, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Harashima, K. Sakata, K. Funato, and H. Kiwada, “Enhanced hepatic uptake of liposomes through complement activation depending on the size of liposomes,” Pharmaceutical Research, vol. 11, no. 3, pp. 402–406, 1994. View at Publisher · View at Google Scholar · View at Scopus
  26. H.-F. Liang, C.-T. Chen, S.-C. Chen et al., “Paclitaxel-loaded poly(γ-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer,” Biomaterials, vol. 27, no. 9, pp. 2051–2059, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. P. N. Gupta, S. Mahor, A. Rawat, K. Khatri, A. Goyal, and S. P. Vyas, “Lectin anchored stabilized biodegradable nanoparticles for oral immunization. 1. Development and in vitro evaluation,” International Journal of Pharmaceutics, vol. 318, no. 1-2, pp. 163–173, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. D. C. Bibby, J. E. Talmadge, M. K. Dalal et al., “Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice,” International Journal of Pharmaceutics, vol. 293, no. 1-2, pp. 281–290, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Stella, S. Arpicco, M. T. Peracchia, et al., “Design of folic acid-conjugated nanoparticles for drug targeting,” Journal of Pharmaceutical Sciences, vol. 89, no. 11, pp. 1452–1464, 2000.
  30. D. L. Iden and T. M. Allen, “In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach,” Biochimica et Biophysica Acta, vol. 1513, no. 2, pp. 207–216, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. D. L. Iden and T. M. Allen, “In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach,” Biochimica et Biophysica Acta, vol. 1513, no. 2, pp. 207–216, 2001. View at Publisher · View at Google Scholar · View at Scopus
  32. B. Schechter, R. Arnon, Y. E. Freedman, L. Chen, and M. Wilchek, “Liver accumulation of TNP-modified streptavidin and avidin: potential use for targeted radio- and chemotherapy,” Journal of Drug Targeting, vol. 4, no. 3, pp. 171–179, 1996. View at Scopus
  33. T. Ouchi, E. Yamabe, K. Hara, M. Hirai, and Y. Ohya, “Design of attachment type of drug delivery system by complex formation of avidin with biotinyl drug model and biotinyl saccharide,” Journal of Controlled Release, vol. 94, no. 2-3, pp. 281–291, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Mamede, T. Saga, T. Ishimori et al., “Hepatocyte targeting of 111In-labeled oligo-DNA with avidin or avidin-dendrimer complex,” Journal of Controlled Release, vol. 95, no. 1, pp. 133–141, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. X. Zeng, Y.-X. Sun, X.-Z. Zhang, and R.-X. Zhuo, “Biotinylated disulfide containing PEI/avidin bioconjugate shows specific enhanced transfection efficiency in HepG2 cells,” Organic and Biomolecular Chemistry, vol. 7, no. 20, pp. 4201–4210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Marysael, M. Bauwens, Y. Ni, G. Bormans, J. Rozenski, and P. de Witte, “Pretargeting of necrotic tumors with biotinylated hypericin using 123I-labeled avidin: evaluation of a two-step strategy,” Investigational New Drugs, vol. 30, no. 6, pp. 2132–2140, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. S.-N. Wang, Y.-H. Deng, H. Xu, H.-B. Wu, Y.-K. Qiu, and D.-W. Chen, “Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 62, no. 1, pp. 32–38, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. Y.-I. Jeong, S.-J. Seo, I.-K. Park et al., “Cellular recognition of paclitaxel-loaded polymeric nanoparticles composed of poly(γ-benzyl L-glutamate) and poly(ethylene glycol) diblock copolymer endcapped with galactose moiety,” International Journal of Pharmaceutics, vol. 296, no. 1-2, pp. 151–161, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Hattori, S. Kawakami, S. Suzuki, F. Yamashita, and M. Hashida, “Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice,” Biochemical and Biophysical Research Communications, vol. 317, no. 4, pp. 992–999, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. P. Opanasopit, M. Sakai, M. Nishikawa, S. Kawakami, F. Yamashita, and M. Hashida, “Inhibition of liver metastasis by targeting of immunomodulators using mannosylated liposome carriers,” Journal of Controlled Release, vol. 80, no. 1–3, pp. 283–294, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. Q. Tian, W. Wang, X. He, et al., “Glycyrrhetinic acid-modified nanoparticles for drug delivery: preparation and characterization,” Chinese Science Bulletin, vol. 54, no. 18, pp. 3121–3126, 2009. View at Publisher · View at Google Scholar
  42. Q. Tian, C.-N. Zhang, X.-H. Wang et al., “Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery,” Biomaterials, vol. 31, no. 17, pp. 4748–4756, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. G. Ashwell and J. Harford, “Carbohydrate-specific receptors of the liver,” Annual Review of Biochemistry, vol. 51, pp. 531–554, 1982. View at Scopus
  44. J. U. Baenziges and D. Fiete, “Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes,” Cell, vol. 22, no. 2, part 2, pp. 611–620, 1980. View at Scopus
  45. A. Kobayashi, M. Goto, K. Kobayashi, and T. Akaike, “Receptor-mediated regulation of differentiation and proliferation of hepatocytes by synthetic polymer model of asialoglycoprotein,” Journal of Biomaterials Science. Polymer Edition, vol. 6, no. 4, pp. 325–342, 1994. View at Scopus
  46. H. Ise, N. Sugihara, N. Negishi, T. Nikaido, and T. Akaike, “Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes,” Biochemical and Biophysical Research Communications, vol. 285, no. 2, pp. 172–182, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. C. S. Cho, M. Goto, A. Kobayashi, K. Kobayashi, and T. Akaike, “Effect of ligand orientation on hepatocyte attachment onto the poly(N-p-vinylbenzyl-o-β-D-galactopyranosyl-D-gluconamide) as a model ligand of asialoglycoprotein,” Journal of Biomaterials Science, Polymer Edition, vol. 7, no. 12, pp. 1097–1104, 1996. View at Scopus
  48. Y. Iwamaru, Y. Shimizu, M. Imamura et al., “Lactoferrin induces cell surface retention of prion protein and inhibits prion accumulation,” Journal of Neurochemistry, vol. 107, no. 3, pp. 636–646, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. A. Suzuki, V. Lopez, and B. Lönnerdal, “Mammalian lactoferrin receptors: structure and function,” Cellular and Molecular Life Sciences, vol. 62, no. 22, pp. 2560–2575, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. P. P. Ward, S. Uribe-Luna, and O. M. Conneely, “Lactoferrin and host defense,” Biochemistry and Cell Biology, vol. 80, no. 1, pp. 95–102, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Huang, W. Ke, Y. Liu, C. Jiang, and Y. Pei, “The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain,” Biomaterials, vol. 29, no. 2, pp. 238–246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. H. Chen, L. Tang, Y. Qin et al., “Lactoferrin-modified procationic liposomes as a novel drug carrier for brain delivery,” European Journal of Pharmaceutical Sciences, vol. 40, no. 2, pp. 94–102, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Wei, Y. Xu, Q. Zou et al., “Hepatocellular carcinoma targeting effect of PEGylated liposomes modified with lactoferrin,” European Journal of Pharmaceutical Sciences, vol. 46, no. 3, pp. 131–141, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Gorria, X. Tekpli, M. Rissel et al., “A new lactoferrin- and iron-dependent lysosomal death pathway is induced by benzo[a]pyrene in hepatic epithelial cells,” Toxicology and Applied Pharmacology, vol. 228, no. 2, pp. 212–224, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. D. J. Bennatt and D. D. McAbee, “Identification and isolation of a 45-kKa calcium-dependent lactoferrin receptor from rat hepatocytes,” Biochemistry, vol. 36, no. 27, pp. 8359–8366, 1997. View at Publisher · View at Google Scholar · View at Scopus
  56. D. J. Bennatt, Y. Y. Ling, and D. D. McAbee, “Isolated rat hepatocytes bind lactoferrins by the RHL-1 subunit of the asialoglycoprotein receptor in a galactose-independent manner,” Biochemistry, vol. 36, no. 27, pp. 8367–8376, 1997. View at Publisher · View at Google Scholar · View at Scopus
  57. D. D. McAbee, X. Jiang, and K. B. Walsh, “Lactoferrin binding to the rat asialoglycoprotein receptor requires the receptor's lectin properties,” Biochemical Journal, vol. 348, no. 1, pp. 113–117, 2000. View at Publisher · View at Google Scholar · View at Scopus
  58. D. D. McAbee, D. J. Bennatt, and Y. Y. L. Yuan Yuan Ling, “Identification and analysis of a CA2+-dependent lactoferrin receptor in rat liver: lactoferrin binds to the asialoglycoprotein receptor in a galactose-independent manner,” Advances in Experimental Medicine and Biology, vol. 443, pp. 113–121, 1998. View at Scopus
  59. A. Pathak, S. P. Vyas, and K. C. Gupta, “Nano-vectors for efficient liver specific gene transfer,” International Journal of Nanomedicine, vol. 3, no. 1, pp. 31–49, 2008. View at Scopus
  60. K. M. Kamruzzaman Selim, Y.-S. Ha, S.-J. Kim et al., “Surface modification of magnetite nanoparticles using lactobionic acid and their interaction with hepatocytes,” Biomaterials, vol. 28, no. 4, pp. 710–716, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. K. M. Kamruzzaman Selim, Z.-C. Xing, H. Guo, and I.-K. Kang, “Immobilization of lactobionic acid on the surface of cadmium sulfide nanoparticles and their interaction with hepatocytes,” Journal of Materials Science, vol. 20, no. 9, pp. 1945–1953, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Díez, G. Navarro, and C. T. de ILarduya, “In vivo targeted gene delivery by cationic nanoparticles for treatment of hepatocellular carcinoma,” Journal of Gene Medicine, vol. 11, no. 1, pp. 38–45, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. Y. Maitani, K. Kawano, K. Yamada, T. Nagai, and K. Takayama, “Efficiency of liposomes surface-modified with soybean-derived sterylglucoside as a liver targeting carrier in HepG2 cells,” Journal of Controlled Release, vol. 75, no. 3, pp. 381–389, 2001. View at Publisher · View at Google Scholar · View at Scopus
  64. X.-R. Qi, W.-W. Yan, and J. Shi, “Hepatocytes targeting of cationic liposomes modified with soybean sterylglucoside and polyethylene glycol,” World Journal of Gastroenterology, vol. 11, no. 32, pp. 4947–4952, 2005. View at Scopus
  65. J. Shi, X.-R. Qi, L. Yang, R. Fei, and L. Wei, “Liver targeting of cationic liposomes modified with soybean-derived sterylglucoside in vitro,” Yaoxue Xuebao, vol. 41, no. 1, pp. 19–23, 2006. View at Scopus
  66. M. Negishi, A. Irie, N. Nagata, and A. Ichikawa, “Specific binding of glycyrrhetinic acid to the rat liver membrane,” Biochimica et Biophysica Acta, vol. 1066, no. 1, pp. 77–82, 1991. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Clerc, V. Sbarra, D. Botta-Fridlund et al., “Bile salt secretion by hepatocytes incubated with bile salts and liposomes or low density lipoproteins,” Life Sciences, vol. 56, no. 4, pp. 277–286, 1995. View at Publisher · View at Google Scholar · View at Scopus
  68. G. Pütz, W. Schmider, R. Nitschke, G. Kurz, and H. E. Blum, “Synthesis of phospholipid-conjugated bile salts and interaction of bile salt-coated liposomes with cultured hepatocytes,” Journal of Lipid Research, vol. 46, no. 11, pp. 2325–2338, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. G. G. Sahagian, J. Distler, and G. W. Jourdian, “Characterization of a membrane-associated receptor from bovine liver that binds phosphomannosyl residues of bovine testicular beta-galactosidase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 7, pp. 4289–4293, 1981. View at Scopus
  70. A. Jayasree, S. Sasidharan, M. Koyakutty, S. Nair, and D. Menon, “Mannosylated chitosan-zinc sulphide nanocrystals as fluorescent bioprobes for targeted cancer imaging,” Carbohydrate Polymers, vol. 85, no. 1, pp. 37–43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Rieger, H. Freichels, A. Imberty et al., “Polyester nanoparticles presenting mannose residues: toward the development of new vaccine delivery systems combining biodegradability and targeting properties,” Biomacromolecules, vol. 10, no. 3, pp. 651–657, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Kawakami, A. Sato, M. Nishikawa, F. Yamashita, and M. Hashida, “Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes,” Gene Therapy, vol. 7, no. 4, pp. 292–299, 2000. View at Scopus
  73. P. Muriel, M. G. Moreno, M. D. C. Hernández, E. Chávez, and L. K. Alcantar, “Resolution of liver fibrosis in chronic CCl4 administration in the rat after discontinuation of treatment: effect of silymarin, silibinin, colchicine and trimethylcolchicinic acid,” Basic and Clinical Pharmacology and Toxicology, vol. 96, no. 5, pp. 375–380, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Suojanen, S.-T. Vilen, P. Nyberg et al., “Selective gelatinase inhibitor peptide is effective in targeting tongue carcinoma cell tumors in vivo,” Anticancer Research, vol. 31, no. 11, pp. 3659–3664, 2011. View at Scopus
  75. Z. Shen, W. Wei, H. Tanaka et al., “A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy,” Pharmacological Research, vol. 64, no. 4, pp. 410–419, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. L. Beljaars, K. Poelstra, G. Molema, and D. K. F. Meijer, “Targeting of sugar- and charge-modified albumins to fibrotic rat livers: the accessibility of hepatic cells after chronic bile duct ligation,” Journal of Hepatology, vol. 29, no. 4, pp. 579–588, 1998. View at Publisher · View at Google Scholar · View at Scopus
  77. E. A. L. Biessen, D. M. Beuting, H. Vietsch, M. K. Bijsterbosch, and T. J. C. Van Berkel, “Specific targeting of the antiviral drug 5-Iodo 2'-deoxyuridine to the parenchymal liver cell using lactosylated poly-L-lysine,” Journal of Hepatology, vol. 21, no. 5, pp. 806–815, 1994. View at Publisher · View at Google Scholar · View at Scopus
  78. B. Schechter, L. Chen, R. Arnon, and M. Wilchek, “Organ selective delivery using a tissue-directed sreptavidin-biotin system: targeting 5-fluorouridine via TNP-streptavidin,” Journal of Drug Targeting, vol. 6, no. 5, pp. 337–348, 1999. View at Scopus
  79. L. Yuan, J. Wang, and W.-C. Shen, “Reversible lipidization of somatostatin analogues for the liver targeting,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 70, no. 2, pp. 615–620, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. J.-H. Han, Y.-K. Oh, D.-S. Kim, and C.-K. Kim, “Enhanced hepatocyte uptake and liver targeting of methotrexate using galactosylated albumin as a carrier,” International Journal of Pharmaceutics, vol. 188, no. 1, pp. 39–47, 1999. View at Publisher · View at Google Scholar · View at Scopus
  81. D.-Q. Wu, B. Lu, C. Chang et al., “Galactosylated fluorescent labeled micelles as a liver targeting drug carrier,” Biomaterials, vol. 30, no. 7, pp. 1363–1371, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Zhang, C. Li, Z.-Y. Xue et al., “Fabrication of lactobionic-loaded chitosan microcapsules as potential drug carriers targeting the liver,” Acta Biomaterialia, vol. 7, no. 4, pp. 1665–1673, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. D. Bhadra, A. K. Yadav, S. Bhadra, and N. K. Jain, “Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting,” International Journal of Pharmaceutics, vol. 295, no. 1-2, pp. 221–233, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. C. M. Sandrine, “Targeting approaches,” in Nanotherapeutics, pp. 67–89, Pan Stanford Publishing, 2008.
  85. R. Zhao, S. Liu, S. Mao, and Y. Wang, “Study on liver targeting effect of vinegar-baked Radix Bupleuri on resveratrol in mice,” Journal of Ethnopharmacology, vol. 126, no. 3, pp. 415–420, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. L. Chen, B. Schechter, R. Arnon, and M. Wilchek, “Tissue selective affinity targeting using the avidin-biotin system,” Drug Development Research, vol. 50, no. 3-4, pp. 258–271, 2000. View at Scopus
  87. G. Di Stefano, C. Busi, M. Derenzini, D. Trerè, and L. Fiume, “Conjugation of 5-fluoro-2′-deoxyuridine with lactosaminated poly-1-lysine to reduce extrahepatic toxicity in the treatment of hepatocarcinomas,” Italian Journal of Gastroenterology and Hepatology, vol. 30, no. 2, pp. 173–177, 1998. View at Scopus
  88. V. P. Torchilin, “Drug targeting,” European Journal of Pharmaceutical Sciences, vol. 11, no. 2, pp. S81–S91, 2000. View at Publisher · View at Google Scholar · View at Scopus
  89. M. K. Bijsterbosch, H. Van De Bilt, and T. J. C. Van Berkel, “Specific targeting of a lipophilic prodrug of iododeoxyuridine to parenchymal liver cells using lactosylated reconstituted high density lipoprotein particles,” Biochemical Pharmacology, vol. 52, no. 1, pp. 113–121, 1996. View at Publisher · View at Google Scholar · View at Scopus
  90. A. M. Dierling and Z. Cui, “Targeting primaquine into liver using chylomicron emulsions for potential vivax malaria therapy,” International Journal of Pharmaceutics, vol. 303, no. 1-2, pp. 143–152, 2005. View at Publisher · View at Google Scholar · View at Scopus
  91. L. F. Lai and H. X. Guo, “Preparation of new 5-fluorouracil-loaded zein nanoparticles for liver targeting,” International Journal of Pharmaceutics, vol. 404, no. 1-2, pp. 317–323, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. L. Beljaars, “Albumin modified with mannose 6-phosphate: a potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells,” Hepatology, vol. 29, no. 5, pp. 1486–1493, 1999. View at Publisher · View at Google Scholar · View at Scopus
  93. B. Wang, W. Li, K. Guo, Y. Xiao, Y. Wang, and J. Fan, “MiR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients,” Biochemical and Biophysical Research Communications, vol. 421, no. 1, pp. 4–8, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. L. J. Elrick, V. Leel, M. G. Blaylock et al., “Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells—a potential mechanism for targeting liver anti-fibrotic therapeutics,” Journal of Hepatology, vol. 42, no. 6, pp. 888–896, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. W. Huang, W. Wang, P. Wang et al., “Glycyrrhetinic acid-modified poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate) micelles for liver targeting therapy,” Acta Biomaterialia, vol. 6, no. 10, pp. 3927–3935, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. X. Li, Q. Wu, Z. Chen, X. Gong, and X. Lin, “Preparation, characterization and controlled release of liver-targeting nanoparticles from the amphiphilic random copolymer,” Polymer, vol. 49, no. 22, pp. 4769–4775, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. P. Ma, S. Liu, Y. Huang, X. Chen, L. Zhang, and X. Jing, “Lactose mediated liver-targeting effect observed by ex vivo imaging technology,” Biomaterials, vol. 31, no. 9, pp. 2646–2654, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Gonzalo, E. G. Talman, A. Van De Ven et al., “Selective targeting of pentoxifylline to hepatic stellate cells using a novel platinum-based linker technology,” Journal of Controlled Release, vol. 111, no. 1-2, pp. 193–203, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. H.-L. Jiang, J.-T. Kwon, E.-M. Kim et al., “Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting,” Journal of Controlled Release, vol. 131, no. 2, pp. 150–157, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Hashida, M. Nishikawa, and Y. Takakura, “Hepatic targeting of drugs and proteins by chemical modification,” Journal of Controlled Release, vol. 36, no. 1-2, pp. 99–107, 1995. View at Publisher · View at Google Scholar · View at Scopus
  101. Y. Xu, X. Jin, Q. Ping et al., “A novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery,” Journal of Controlled Release, vol. 146, no. 3, pp. 299–308, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Hu, Y. Shen, B. Ji et al., “Liver-specific gene therapy of hepatocellular carcinoma by targeting human telomerase reverse transcriptase with pegylated immuno-lipopolyplexes,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 78, no. 3, pp. 320–325, 2011. View at Publisher · View at Google Scholar · View at Scopus
  103. P. J. Swart, T. Hirano, M. E. Kuipers et al., “Targeting of superoxide dismutase to the liver results in anti- inflammatory effects in rats with fibrotic livers,” Journal of Hepatology, vol. 31, no. 6, pp. 1034–1043, 1999. View at Publisher · View at Google Scholar · View at Scopus
  104. Y. Hattori, S. Kawakami, F. Yamashita, and M. Hashida, “Controlled biodistribution of galactosylated liposomes and incorporated probucol in hepatocyte-selective drug targeting,” Journal of Controlled Release, vol. 69, no. 3, pp. 369–377, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. F. Danhier, B. Vroman, N. Lecouturier et al., “Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with Paclitaxel,” Journal of Controlled Release, vol. 140, no. 2, pp. 166–173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. F. Li, J.-Y. Sun, J.-Y. Wang et al., “Effect of hepatocyte growth factor encapsulated in targeted liposomes on liver cirrhosis,” Journal of Controlled Release, vol. 131, no. 1, pp. 77–82, 2008. View at Publisher · View at Google Scholar · View at Scopus
  107. G. Huang, J. Diakur, Z. Xu, and L. I. Wiebe, “Asialoglycoprotein receptor-targeted superparamagnetic iron oxide nanoparticles,” International Journal of Pharmaceutics, vol. 360, no. 1-2, pp. 197–203, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. J. H. Maeng, D.-H. Lee, K. H. Jung et al., “Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer,” Biomaterials, vol. 31, no. 18, pp. 4995–5006, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Becker, M. Spiess, and H.-D. Klenk, “The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus,” Journal of General Virology, vol. 76, no. 2, pp. 393–399, 1995. View at Scopus
  110. X.-Q. Zhang, X.-L. Wang, P.-C. Zhang et al., “Galactosylated ternary DNA/polyphosphoramidate nanoparticles mediate high gene transfection efficiency in hepatocytes,” Journal of Controlled Release, vol. 102, no. 3, pp. 749–763, 2005. View at Publisher · View at Google Scholar · View at Scopus
  111. M. Singh and M. Ariatti, “Targeted gene delivery into HepG2 cells using complexes containing DNA, cationized asialoorosomucoid and activated cationic liposomes,” Journal of Controlled Release, vol. 92, no. 3, pp. 383–394, 2003. View at Publisher · View at Google Scholar · View at Scopus
  112. T. Shinoda, A. Maeda, S. Kagatani et al., “Specific interaction between galactose branched-cyclodextrins and hepatocytes in vitro,” International Journal of Pharmaceutics, vol. 167, no. 1-2, pp. 147–154, 1998. View at Publisher · View at Google Scholar · View at Scopus
  113. H. Harashima and H. Kiwada, “Liposomal targeting and drug delivery: kinetic consideration,” Advanced Drug Delivery Reviews, vol. 19, no. 3, pp. 425–444, 1996. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Lin, Y. Liu, Y. Huang et al., “Glycyrrhizin surface-modified chitosan nanoparticles for hepatocyte-targeted delivery,” International Journal of Pharmaceutics, vol. 359, no. 1-2, pp. 247–253, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. Q. Tian, C.-N. Zhang, X.-H. Wang et al., “Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery,” Biomaterials, vol. 31, no. 17, pp. 4748–4756, 2010. View at Publisher · View at Google Scholar · View at Scopus
  116. S. E. Gratton, P. A. Ropp, P. D. Pohlhaus, et al., “The effect of particle design on cellular internalization pathways,” Proceedings of the National Academy of Sciences of USA, vol. 105, no. 33, pp. 11613–11618, 2008. View at Publisher · View at Google Scholar
  117. G. Sharma, D. T. Valenta, Y. Altman et al., “Polymer particle shape independently influences binding and internalization by macrophages,” Journal of Controlled Release, vol. 147, no. 3, pp. 408–412, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. Y. Geng, P. Dalhaimer, S. Cai et al., “Shape effects of filaments versus spherical particles in flow and drug delivery,” Nature Nanotechnology, vol. 2, no. 4, pp. 249–255, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. S.-Y. Lin, W.-H. Hsu, J.-M. Lo, H.-C. Tsai, and G.-H. Hsiue, “Novel geometry type of nanocarriers mitigated the phagocytosis for drug delivery,” Journal of Controlled Release, vol. 154, no. 1, pp. 84–92, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. A. Arnida, M. M. Janát-Amsbury, A. Ray, C. M. Peterson, and H. Ghandehari, “Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 77, no. 3, pp. 417–423, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. P. Decuzzi, B. Godin, T. Tanaka et al., “Size and shape effects in the biodistribution of intravascularly injected particles,” Journal of Controlled Release, vol. 141, no. 3, pp. 320–327, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. N. Doshi, B. Prabhakarpandian, A. Rea-Ramsey, K. Pant, S. Sundaram, and S. Mitragotri, “Flow and adhesion of drug carriers in blood vessels depend on their shape: a study using model synthetic microvascular networks,” Journal of Controlled Release, vol. 146, no. 2, pp. 196–200, 2010. View at Publisher · View at Google Scholar · View at Scopus
  123. Z. Liu, W. Cai, L. He et al., “In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice,” Nature Nanotechnology, vol. 2, no. 1, pp. 47–52, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. K. A. Beningo and Y.-L. Wang, “Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target,” Journal of Cell Science, vol. 115, no. 4, pp. 849–856, 2002. View at Scopus
  125. C. Yamashita, H. Matsuo, K. Akiyama, and H. Kiwada, “Enhancing effect of cetylmannoside on targeting of liposomes to Kupffer cells in rats,” International Journal of Pharmaceutics, vol. 70, no. 3, pp. 225–233, 1991. View at Publisher · View at Google Scholar · View at Scopus
  126. B. N. Melgert, P. Olinga, J. M. S. Van Der Laan et al., “Targeting dexamethasone to Kupffer cells: effects on liver inflammation and fibrosis in rats,” Hepatology, vol. 34, no. 4, pp. 719–728, 2001. View at Publisher · View at Google Scholar · View at Scopus
  127. T. J. Merkel, S. W. Jones, K. P. Herlihy et al., “Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 2, pp. 586–591, 2011. View at Publisher · View at Google Scholar · View at Scopus
  128. H. Hillaireau and P. Couvreur, “Nanocarriers' entry into the cell: relevance to drug delivery,” Cellular and Molecular Life Sciences, vol. 66, no. 17, pp. 2873–2896, 2009. View at Publisher · View at Google Scholar · View at Scopus
  129. D. Schuppan, M. Ruehl, R. Somasundaram, and E. G. Hahn, “Matrix as a modulator of hepatic fibrogenesis,” Seminars in Liver Disease, vol. 21, no. 3, pp. 351–372, 2001. View at Publisher · View at Google Scholar · View at Scopus
  130. R. C. Benyon and M. J. P. Arthur, “Extracellular matrix degradation and the role of hepatic stellate cells,” Seminars in Liver Disease, vol. 21, no. 3, pp. 373–384, 2001. View at Publisher · View at Google Scholar · View at Scopus
  131. D. C. Rockey, “Hepatic blood flow regulation by stellate cells in normal and injured liver,” Seminars in Liver Disease, vol. 21, no. 3, pp. 337–349, 2001. View at Publisher · View at Google Scholar · View at Scopus
  132. M. Lück, B. R. Paulke, W. Schröder, T. Blunk, and R. H. Müller, “Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics,” Journal of Biomedical Materials Research, vol. 39, no. 3, pp. 478–485, 1998.
  133. R. Greupink, H. I. Bakker, C. Reker-Smit et al., “Studies on the targeted delivery of the antifibrogenic compound mycophenolic acid to the hepatic stellate cell,” Journal of Hepatology, vol. 43, no. 5, pp. 884–892, 2005. View at Publisher · View at Google Scholar · View at Scopus
  134. J. E. Adrian, J. A. A. M. Kamps, G. L. Scherphof et al., “A novel lipid-based drug carrier targeted to the non-parenchymal cells, including hepatic stellate cells, in the fibrotic livers of bile duct ligated rats,” Biochimica et Biophysica Acta, vol. 1768, no. 6, pp. 1430–1439, 2007. View at Publisher · View at Google Scholar · View at Scopus
  135. A. Raz, C. Bucana, and W. E. Fogler, “Biochemical, morphological, and ultrastructural studies on the uptake of liposomes by murine macrophages,” Cancer Research, vol. 41, no. 2, pp. 487–494, 1981. View at Scopus
  136. A. Chonn, S. C. Semple, and P. R. Cullis, “Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes,” Journal of Biological Chemistry, vol. 267, no. 26, pp. 18759–18765, 1992. View at Scopus
  137. K. Xiao, Y. Li, J. Luo et al., “The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles,” Biomaterials, vol. 32, no. 13, pp. 3435–3446, 2011. View at Publisher · View at Google Scholar · View at Scopus
  138. A. Mori, A. L. Klibanov, V. P. Torchilin, and L. Huang, “Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo,” FEBS Letters, vol. 284, no. 2, pp. 263–266, 1991. View at Publisher · View at Google Scholar · View at Scopus
  139. A. Gabizon and D. Papahadjopoulos, “Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 18, pp. 6949–6953, 1988. View at Scopus
  140. D. Peer and R. Margalit, “Tumor-targeted hyaluronan nanoliposomes increase the antitumor activity of liposomal doxorubicin in syngeneic and human xenograft mouse tumor models,” Neoplasia, vol. 6, no. 4, pp. 343–353, 2004. View at Publisher · View at Google Scholar · View at Scopus
  141. D. Liu, F. Liu, and Y. K. Song, “Monosialoganglioside GM1 shortens the blood circulation time of liposomes in rats,” Pharmaceutical Research, vol. 12, no. 4, pp. 508–512, 1995. View at Scopus
  142. D. Liu, Y. K. Song, and F. Liu, “Antibody dependent, complement mediated liver uptake of liposomes containing GM1,” Pharmaceutical Research, vol. 12, no. 11, pp. 1775–1780, 1995. View at Publisher · View at Google Scholar · View at Scopus
  143. D. Liu, Q. Hu, and Y. K. Song, “Liposome clearance from blood: different animal species have different mechanisms,” Biochimica et Biophysica Acta, vol. 1240, no. 2, pp. 277–284, 1995. View at Publisher · View at Google Scholar · View at Scopus
  144. A. Rigotti, S. L. Acton, and M. Krieger, “The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids,” Journal of Biological Chemistry, vol. 270, no. 27, pp. 16221–16224, 1995. View at Publisher · View at Google Scholar · View at Scopus
  145. Q. Yu, R. Shao, H. S. Qian, S. E. George, and D. C. Rockey, “Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension,” Journal of Clinical Investigation, vol. 105, no. 6, pp. 741–748, 2000. View at Scopus
  146. Z. Qi, N. Atsuchi, A. Ooshima, A. Takeshita, and H. Ueno, “Blockade of type β transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 5, pp. 2345–2349, 1999. View at Publisher · View at Google Scholar · View at Scopus
  147. K. L. Rudolph, S. Chang, M. Millard, N. Schreiber-Agus, and R. A. DePinho, “Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery,” Science, vol. 287, no. 5456, pp. 1253–1258, 2000. View at Publisher · View at Google Scholar · View at Scopus
  148. S. Salgado, J. Garcia, J. Vera et al., “Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy,” Molecular Therapy, vol. 2, no. 6, pp. 545–551, 2000. View at Publisher · View at Google Scholar · View at Scopus
  149. V. Terpstra and T. J. C. Van Berkel, “Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice,” Blood, vol. 95, no. 6, pp. 2157–2163, 2000. View at Scopus
  150. C. D. Oja, S. C. Semple, A. Chonn, and P. R. Cullis, “Influence of dose on liposome clearance: critical role of blood proteins,” Biochimica et Biophysica Acta, vol. 1281, no. 1, pp. 31–37, 1996. View at Publisher · View at Google Scholar · View at Scopus
  151. T. M. Allen and C. Hansen, “Pharmacokinetics of stealth versus conventional liposomes: effect of dose,” Biochimica et Biophysica Acta, vol. 1068, no. 2, pp. 133–141, 1991. View at Publisher · View at Google Scholar · View at Scopus
  152. Z. Panagi, A. Beletsi, G. Evangelatos, E. Livaniou, D. S. Ithakissios, and K. Avgoustakis, “Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles,” International Journal of Pharmaceutics, vol. 221, no. 1-2, pp. 143–152, 2001. View at Publisher · View at Google Scholar · View at Scopus
  153. D. D. Chow, H. E. Essien, M. M. Padki, and K. J. Hwang, “Targeting small unilamellar liposomes to hepatic parenchymal cells by dose effect,” Journal of Pharmacology and Experimental Therapeutics, vol. 248, no. 2, pp. 506–513, 1989. View at Scopus
  154. E. W. M. Van Etten, M. T. Ten Kate, S. V. Snijders, and I. A. J. M. Bakker-Woudenberg, “Administration of liposomal agents and blood clearance capacity of the mononuclear phagocyte system,” Antimicrobial Agents and Chemotherapy, vol. 42, no. 7, pp. 1677–1681, 1998. View at Scopus
  155. H. Harashima, K. Sakata, and H. Kiwada, “Distinction between the depletion of opsonins and the saturation of uptake in the dose-dependent hepatic uptake of liposomes,” Pharmaceutical Research, vol. 10, no. 4, pp. 606–610, 1993. View at Publisher · View at Google Scholar · View at Scopus
  156. A. Gabizon, D. Tzemach, L. Mak, M. Bronstein, and A. T. Horowitz, “Dose dependency of pharmacokinetics and therapeutic efficacy of pegylated liposomal doxorubicin (DOXIL) in murine models,” Journal of Drug Targeting, vol. 10, no. 7, pp. 539–548, 2002. View at Publisher · View at Google Scholar · View at Scopus
  157. T. L. Andresen, S. S. Jensen, and K. Jørgensen, “Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release,” Progress in Lipid Research, vol. 44, no. 1, pp. 68–97, 2005. View at Publisher · View at Google Scholar · View at Scopus
  158. F. Chellat, Y. Merhi, A. Moreau, and L. Yahia, “Therapeutic potential of nanoparticulate systems for macrophage targeting,” Biomaterials, vol. 26, no. 35, pp. 7260–7275, 2005. View at Publisher · View at Google Scholar · View at Scopus
  159. P. L. Williams and H. Gray, Gray's Anatomy: The Anatomical Basis of Medicine and Surgery, Churchill Livingstone, 1995.
  160. Body Atlas, Octopus Books, 2008.
  161. A. C. Guyton, Textbook of Medical Physiology, Saunders, 1981.
  162. M. Cheng, B. He, T. Wan, et al., “5-Fluorouracil nanoparticles inhibit hepatocellular carcinoma via activation of the p53 pathway in the orthotopic transplant mouse model,” PLoS One, vol. 7, no. 10, article e47115, 2012.
  163. X. Li, H. Xu, X. Dai, Z. Zhu, B. Liu, and X. Lu, “Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer,” International Journal of Nanomedicine, vol. 7, pp. 5183–5190, 2012.
  164. X. Zhou, M. Zhang, B. Yung, et al., “Lactosylated liposomes for targeted delivery of doxorubicin to hepatocellular carcinoma,” International Journal of Nanomedicine, vol. 7, pp. 5465–5474, 2012.
  165. X. Zhang, X. Zhang, P. Yu, et al., “Hydrotropic polymeric mixed micelles based on functional hyperbranched polyglycerol copolymers as hepatoma-targeting drug delivery system,” Journal of Pharmaceutical Sciences, vol. 102, no. 1, pp. 145–1453, 2013.