Is there a clinical future for polymeric nanoparticles as brain-targeting drug delivery agents?

Drug Discovery Today

Volumn 17, Issue 7-8, 2012, Pages 367-378

  Costantino, Luca ^a   Boraschi, Diana ^b  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^b CNR   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 B 3101; 2 B 3201; AGT 181; AGT 190; ALBUMIN; ANG 1004; ANG 1005; ANG 1011; ANG 2002; ANG 2008; ANGIOPEP 2 PEPTIDE; BIND 014; CALAA 01; CAMPTOTHECIN; COG 197; CYANOACRYLATE; CYCLODEXTRIN; DENDRIMER; DOCETAXEL; DOXORUBICIN; GRN 1005; HYBRID PROTEIN; IRINOTECAN; IT 101; LIPID; LIPOBRIDGE; LIPOSOME; LIVITAG; MELANOTRANSFERRIN; MITOXANTRONE; MONOCLONAL ANTIBODY; NANOCARRIER; NANOPARTICLE; NLCPT 11; PACLITAXEL; PACLITAXEL POLIGLUMEX; PEPTIDE DERIVATIVE; PEPTIDE RAP; POLYAMIDOAMINE; POLYAMINOACID; POLYESTER; POLYGLUTAMIC ACID; POLYMER; R 17217; SMALL INTERFERING RNA; TEKMIRA; TRASCEND; UNCLASSIFIED DRUG; UNINDEXED DRUG; VH 0445; VHO 455 PEPTIDE; VINCRISTINE; VINCRISTINE SULFATE;

BLOOD BRAIN BARRIER; BRAIN TUMOR; BREAST CANCER; CONJUGATE; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG TARGETING; HUMAN; LEUKEMIA; LIVER TUMOR; MACROMOLECULE; MELANOMA; MICELLE; NANOTECHNOLOGY; NONHUMAN; PARTICLE SIZE; PROSTATE CANCER; REVIEW; SOLID TUMOR;

ANIMALS; BRAIN; CLINICAL TRIALS AS TOPIC; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; HUMANS; NANOPARTICLES; POLYMERS;

EID: 84859267208     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2011.10.028     Document Type: Review

References (162)

1. J. Sanchis Polymer-drug conjugates for novel molecular targets Nanomedicine 5 2010 915 935
2. L. Zhang Nanoparticles in medicine: therapeutic applications and developments Clin. Pharmacol. Ther. 83 2008 761 769 (Pubitemid 351556021)
3. R. Gaspar, and R. Duncan Polymeric carriers: preclinical safety and the regulatory implications for design and development of polymer therapeutics Adv. Drug Deliv. Rev. 61 2009 1220 1231
4. F. Alexis Factors affecting the clearance and biodistribution of polymeric nanoparticles Mol. Pharm. 5 2008 505 515
5. O.C. Farokhzad, and R. Langer Impact of nanotechnology on drug delivery ACS Nano 3 2009 16 20
6. M. Di Marco Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation Int. J. Nanomed. 5 2010 37 49
7. S. Martind Lipid-based colloidal carriers for peptide and protein delivery-liposomes versus lipid nanoparticles Int. J. Nanomed. 2 2007 595 607
8. Q. Leng Advances in systemic siRNA delivery Drugs Fut. 34 2009 721 737
9. M.A. Mintzer, and E.E. Simanek Nonviral vectors for gene delivery Chem. Rev. 109 2009 259 302
10. D.J. Begley Delivery of therapeutic agents to the central nervous system: the problems and the possibility Pharm. Ther. 104 2004 29 45 (Pubitemid 39410561)
11. R. Gabathuler Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases Neurobiol. Dis. 37 2010 48 57
12. W.M. Pardridge Biopharmaceutical drug targeting to the brain J. Drug Target. 18 2010 157 167
13. F.I. Staquicini Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma J. Clin. Invest. 121 2011 161 173
14. L. Costantino Peptide-derivatized biodegradable nanoparticles able to cross the blood-brain barrier J Control. Rel. 108 2005 84 96 (Pubitemid 41476677)
15. I. Reimold Delivery of nanoparticles to the brain detected by fluorescence microscopy Eur. J. Pharm. Biopharm. 70 2008 627 632
16. A. Zense Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones J. Control. Rel. 137 2009 78 86
17. A. Cerletti Endocytosis and transcytosis of an immunoliposome-based brain drug delivery system J. Drug Target. 8 2000 435 446 (Pubitemid 32366711)
18. E. Markoutsa Uptake and permeability studies of BBB-targeting immunoliposomes using the hCMEC/D3 cell line Eur. J. Pharm. Biopharm. 77 2011 265 274
19. R.G. Thorne, and C. Nicholson In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space Proc. Natl. Acad. Sci. U. S. A. 103 2006 5567 5572
20. L. Hasadsri Functional protein delivery into neurons using polymeric nanoparticles J. Biol. Chem. 284 2009 6972 6981
21. G.H. Huynh Barriers to carrier mediated drug and gene delivery to brain tumors J. Control. Rel. 110 2006 236 259 (Pubitemid 41827478)
22. F. Kratz, and U. Beyer Serum proteins as drug carriers of anticancer agents: a review Drug Deliv. 5 1998 281 299 (Pubitemid 29031430)
23. R.E. Pitas Lipoproteins and their receptors in the central nervous system J. Biol. Chem. 262 1987 14352 14360
24. F.C. Thomas Uptake of ANG1005, a novel paclitaxel derivative, through the blood-brain barrier into brain and experimental brain metastases of breast cancer Pharm. Res. 26 2009 2486 2494
25. J. Rip Differential receptor-mediated drug targeting to the diseased brain Expert Opin. Drug Deliv. 6 2009 227 237
26. N.J. Abbott Structure and function of the blood-brain barrier Neurobiol. Dis. 37 2010 13 25
27. J.M. Wardlaw Blood-brain barrier and cerebral small vessel disease J. Neurol. Sci. 299 2010 66 71
28. L.A. Lampson Targeted therapy for neuro-oncology: reviewing the menu Drug Discov. Today 14 2009 185 191
29. S.K. Hobbs Regulation of transport pathways in tumor vessels: role of tumor type, and microenvironment Proc. Natl. Acad. Sci. U. S. A. 95 1998 4607 4612 (Pubitemid 28207960)
30. F. Yuan Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft Cancer Res. 54 1994 3352 3356 (Pubitemid 24225946)
31. S.K. Hobbs Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment Proc. Natl. Acad. Sci. U. S. A. 95 1998 4607 4612 (Pubitemid 28207960)
32. H. Sarin Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors J. Transl. Med. 7 2009 77
33. P.R. Lockman Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer Clin. Cancer Res. 16 2010 5664 5678
34. M.J. Vincent Polymer-drug conjugates as modulators of cellular apoptosis AAPS J. 9 2007 22
35. Jeyapalan, S. et al. (2010) Paclitaxel Poliglumex (PPX), temozolamide (TMZ), and radiation (RT) for newly diagnosed high-grade gliomas: a Brown University Oncology Group (BrUOG) Phase II study. Poster presented at Society for Neurooncology (SNO) Scientific Meeting, 18-21 November 2010, Montreal, Canada
36. H. Ding Inhibition of brain tumor growth by intravenous poly(β-l malic acid) nanobioconjugate with pH-dependent drug release Proc. Natl. Acad. Sci. U. S. A. 107 2010 18143 18148
37. W. Ke Gene delivery targeted to the brain using an angiopep-modified polyamidoamine dendrimer Biomaterials 30 2009 6976 6985
38. R.Q. Huang Efficient gene delivery targeted to the brain using a transferrin-conjugated polyethyleneglycol-modified polyamidoamine dendrimer FASEB J. 21 2007 117 125
39. R. Huang The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain Biomaterials 29 2008 238 246 (Pubitemid 350016299)
40. D. Triguero Capillary depletion method for quantification of blood-brain transport of circulating peptides and plasma proteins J. Neurochem. 54 1990 1882 1888
41. M. Demeule Involvement of the low-density lipoprotein-receptor-related protein in the transcytosis of the brain delivery vector angiopep-2 J. Neurochem. 106 2008 1534 1544
42. M. Demeule Identification and design of peptides as a new drug delivery system for the brain J. Pharmacol. Exp. Ther. 324 2008 1064 1072 (Pubitemid 351397849)
43. S.M. Chang A Phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending on the concomitant use of anticonvulsant: a North American Brain Tumor Consortium Report Cancer 91 2001 417 422 (Pubitemid 32099244)
44. Drappatz, J. et al. (2009) ANG1005: development of a new engineered peptide compound (EPiC) for the treatment of malignant glioma. Poster presented at Neuroscience 2009, 18 October, Chicago, IL, available at: http://www.angiochem.com/en/publications
45. Kurzrock, R. et al. (2009) ANG-1005: a promising new engineered peptide compound (EPiC) for patients with advanced solid tumors and brain metastases. Poster presented at Neuroscience 2009, 18 October, Chicago, IL, available at: http://www.angiochem.com/en/publications
46. Drappaz, J. et al. (2010) ANG-1005: results of a Phase I study in patients with recurrent malignant glioma. Poster presented at ASCO annual Meeting 2010, 4-8 June, Chicago IL, available at: http://www.angiochem.com/en/ publications
47. C. Che New angiopep-modified doxorubicin (ANG1007) and Etoposide (ANG1009) chemotherapeutics with increased brain penetration J. Med. Chem. 53 2010 2814 2824
48. Demeule, M. et al. (2010) ANG2002: a new angiochem-modified neurotensin with increased brain penetration and analgesic properties. Poster presented at Neurosciences Meeting, 13-17 November, San Diego, CA, available at: http://www.angiochem.com/en/publications
49. D. Karkan A unique carrier for delivery of therapeutic compounds beyond the blood-brain barrier PLoS One 3 2008 e2469
50. B. Vastag Biotechnology: crossing the barrier Nature 466 2010 916 918
51. A. Fu Intravenous treatment of experimental Parkinson's disease in the mouse with an IgG-GDNF fusion protein that penetrates the blood-brain barrier Brain Res. 1352 2010 208 213
52. A.R. Jones, and E.V. Shusta Blood-brain barrier transport of therapeutics via receptor mediation Pharm. Res. 24 2007 1759 1771 (Pubitemid 47206625)
53. Q.H. Zhou Re-engineering erythropoietin as an IgG fusion protein that penetrates the blood-brain barrier in the mouse Mol. Pharm. 7 2010 2148 2155
54. Q.H. Zhou Delivery of a peptide radiopharmaceutical to brain with an IgG-avidin fusion protein Bioconj. Chem. 22 2011 1611 1618
55. Y.J. Yu Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target Sci. Transl. Med. 3 84 2011 ra44
56. J.K. Atwal A therapeutic antibody targeting BACE1 inhibits amyloid-β production in vivo Sci. Transl. Med. 3 84 2011 ra43
57. I. van Rooy In vivo methods to study uptake of nanoparticles into the brain Pharm. Res. 28 2011 456 471
58. S.V. Vinogradov Nanogels for oligonucleotide delivery to the brain Bioconj. Chem. 15 2004 50 60 (Pubitemid 38165980)
59. S. Wohlfart Kinetics of transport of doxorubicin bound to nanoparticles across the blood-brain barrier J. Control. Rel. 154 2011 103 107
60. B. Wilson Targeted delivery of tacrine into the brain with Polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles Eur. J. Pharm. Biopharm. 70 2008 75 84
61. B. Wilson Poly(n-butylcyanoacrylate) nanoparticles coated with Polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer's disease Brain Res. 1200 2008 159 168
62. K.B. Kurakhmaeva Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles J. Drug Target. 17 2009 564 574
63. X.H. Tian Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles Int. J. Nanomed. 6 2011 445 452
64. K. Hu Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations J. Control. Rel. 134 2009 55 61
65. C.W. Gau Transferrin-conjugated nanoparticles of poly(lactide)-d-α- tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood-brain barrier Biomaterials 31 2010 7748 7757
66. Z. Pang Brain delivery and cellular internalization mechanisms for transferrin conjugated biodegradable polymersomes Int. J. Pharm. 415 2011 284 292
67. K. Hu Lactoferrin-conjugated PEG-PLA nanoparticles for brain delivery: preparation, characterization and efficacy in Parkinson's disease Int. J. Pharm. 415 2011 273 283
68. J. Li Targeting the brain with PEG-PLGA nanoparticles modified with phage-display peptides Biomaterials 32 2011 4943 4950
69. V. Mishra Targeted brain delivery of AZT via transferrin anchored pegylated albumin nanoparticles J. Drug Target. 14 2006 45 53
70. S.C. Yang Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain J. Control. Rel. 59 1999 299 307 (Pubitemid 29238174)
71. Y. Gupta Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain J. Pharm. Pharmacol. 59 2007 935 940 (Pubitemid 47051073)
72. G. Huang Solid lipid nanoparticles of temozolomide: potential reduction of cardial and nephric toxicity Int. J. Pharm. 355 2008 314 320
73. G.P. Zara Intravenous administration to rabbits of non-stealth and stealth doxorubicin-loaded solid lipid nanoparticles at increasing concentrations of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and other organs J. Drug Target. 10 2002 327 335 (Pubitemid 34746314)
74. J. Huwyler Brain drug delivery of small molecules using immunoliposomes Proc. Natl. Acad. Sci. U. S. A. 93 1996 14164 14169 (Pubitemid 26424263)
75. I. van Rooy Comparison of five different targeting ligands to enhance accumulation of liposomes into the brain J. Control. Rel. 150 2010 30 36
76. P. Kandadi Brain specific delivery of pegylated indinavir submicron lipid emulsions Eur. J. Pharm. Sci. 42 2011 423 432
77. K. Shao Angiopep-2 modified PE-PEG based polymeric micelles for amphotericin B delivery targeted to the brain J. Control. Rel. 147 2010 118 126
78. I. van Rooy Identification of peptide ligands for targeting to the blood-brain barrier Pharm. Res. 27 2010 673 682
79. P. Xu Intracellular drug delivery by poly(lactic-to-glycolic acid) nanoparticles, revisited Mol. Pharm. 6 2009 190 201
80. 14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats J. Drug Target. 14 2006 97 105
81. I. Brigger Negative preclinical results with stealth nanospheres- encapsulated Doxorubicin in an orthotopic murine brain tumor model J. Control. Rel. 100 2004 29 40 (Pubitemid 39445983)
82. B. Petri Chemotherapy of brain tumors using doxorubicin bound to surfactant-coated poly(butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants J. Control. Rel. 117 2007 51 58 (Pubitemid 46164866)
83. M. Gaumet Nanoparticles for drug delivery: the need for precision in reporting particle size parameters Eur. J. Pharm. Biopharm. 69 2008 1 9 (Pubitemid 351467152)
84. K. Rausch Evaluation of nanoparticle aggregation in human blood serum Biomacromolecules 11 2010 2836 2839
85. K. Gao, and X. Jiang Influence of particle size on transport of metotrexate across blood brain barrier by polysorbate 80-coated polybutylcyanoacrylate nanoparticles Int. J. Pharm. 310 2006 213 219 (Pubitemid 43287986)
86. K. Ulbrich Transferrin- and transferrin-receptor antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB) Eur. J. Pharm. Biopharm. 71 2009 251 256
87. K. Ulbrich Targeting the insulin receptor: nanoparticles for drug delivery across the blood-brain barrier (BBB) J. Drug Target. 19 2011 125 132
88. K. Michaelis Covalent linkage of apolipoprotein E to albumin nanoparticle strongly enhances drug transport into the brain J. Pharmacol. Exp. Ther. 317 2006 1246 1253 (Pubitemid 43764130)
89. J. Kreuter Covalent attachment of Apolipoprotein A-I and Apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain J. Control. Rel. 118 2007 54 58 (Pubitemid 46283106)
90. H.J. Lee Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse J. Pharmacol. Exp. Ther. 292 2000 1048 1052 (Pubitemid 30136600)
91. T.A. ElBayoumi, and V.P. Torchilin Tumor-targeted nanomedicines: enhanced antitumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancer-specific monoclonal antibody Clin. Cancer Res. 15 2009 1973 1980
92. M.I. Koukorakis High intratumoral accumulation of stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumors Br. J. Cancer 83 2000 1281 1286
93. P. Laverman (99m)Tc-labeled stealth liposomal doxorubicin (Caelyx) in glioblastomas and metastatic brain tumors Br. J. Cancer 86 2002 659 661 (Pubitemid 34185108)
94. K. Fabel Long-termstabilization in patients with malignant glioma after treatment with liposomal doxorubicin Cancer 92 2001 1936 1942 (Pubitemid 32952514)
95. P. Hau Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma Cancer 100 2004 1199 1207 (Pubitemid 38325948)
96. S.L. Chua Phase 2 study of temozolomide and Caelyx in patients with recurrent glioblastoma multiforme NeuroOncology 6 2004 38 43 (Pubitemid 38139638)
97. M. Glas Pegylated liposomal doxorubicin in recurrent malignant glioma: analysis of a case series Oncology 72 2007 302 307 (Pubitemid 351238141)
98. T. Tanaka Tumor targeting based on the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME) Int. J. Pharm. 277 2004 39 61 (Pubitemid 38670420)
99. T.A. ElBayoumi, and V.P. Torchilin Tumor-specific anti-nucleosome antibody improves therapeutic efficacy of doxorubicin-loaded long-circulating liposomes against primary and metastatic tumor in mice Mol. Pharm. 6 2009 246 254
100. H. Hatakeyama Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes Int. J. Pharm. 342 2007 194 200 (Pubitemid 47259319)
101. D.B. Kirpotin Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models Cancer Res. 66 2006 6732 6740 (Pubitemid 44085631)
102. J. Kreuter Nanoparticulate systems for brain delivery of drugs Adv. Drug Deliv. Rev. 47 2001 65 81 (Pubitemid 32209233)
103. M.D. Joshi, and R.H. Muller Lipid nanoparticles for parenteral delivery of actives Eur. J. Pharm. Biopharm. 71 2009 161 172
104. H.R. Kim Translocation of poly(ethylene glycol-co-hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells: role of apolipoproteins in receptor-mediated endocytosis Biomacromolecules 8 2007 793 799 (Pubitemid 46488459)
105. L. Costantino Drug delivery to CNS and polymeric nanoparticulate carriers Fut. Med. Chem. 2 2010 1681 1701
106. R. Rempe Transport of poly(n-butylcyano-acrylate) nanoparticles across the blood-brain barrier in vitro and their influence on barrier integrity Biochem. Biophys. Res. Commun. 406 2011 64 69
107. R.N. Alyautdin Delivery of loperamide across the blood-brain barrier with Polysorbate 80-coated polybutylcyanoacrylate nanoparticles Pharm. Res. 14 1997 325 328 (Pubitemid 27160944)
108. S. Gelperina Drug delivery to the brain using surfactant-coated poly (lactide-co-glycolide) nanoparticles: influence of the formulation parameters Eur. J. Pharm. Biopharm. 74 2010 157 163
109. G. Tosi Targeting the central nervous system: in vivo experiments with peptide-derivatized nanoparticles loaded with loperamide and Rhodamine-123 J. Control. Rel. 122 2007 1 9 (Pubitemid 47284547)
110. G. Tosi Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: in vivo pharmacological evidence and biodistribution J. Control. Rel. 145 2010 49 57
111. R.C. Mundargi Nano/micro technologies for delivering macromolecular therapeutics using poly(dl-lactide-co-glycolide) and its derivatives J. Control. Rel. 125 2008 193 209
112. M.L. De Temmerman Particulate vaccines: on the quest for optimal delivery and immune response Drug Discov. Today 16 2011 569 582
113. J. Panjam, and V. Labhasetwar Sustained cytoplasmatic delivery of drugs with intracellular receptors using biodegradable nanoparticles Mol. Pharm. 1 2004 77 84
114. S. Prabha, and V. Labhasetwar Nanoparticle-mediated wild-type p53 gene delivery results in sustained antiproliferative activity in breast cancer cells Mol. Pharm. 1 2004 211 219
115. K.A. Woodrow Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA Nat. Mater. 8 2009 526 533
116. M. Stern Poly (DL-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo Gene Ther. 10 2003 1282 1288 (Pubitemid 36987118)
117. N.G. On Assessment of P-glycoprotein activity in the blood-brain barrier (BBB) using Near Infrared Fluorescence (NIRF) imaging techniques Pharm. Res. 28 2011 2505 2515
118. E.V. Batrakova, and A.V. Kabanov Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers J. Control. Rel. 130 2008 98 106
119. J. Huang Effect of Pluronic F68 block copolymer on P-glycoprotein transport and CYP3A4 metabolism Int. J. Pharm. 356 2008 351 353
120. K.S. Rao TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs Biomaterials 29 2008 4429 4438
121. Z. Panagi Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles Int. J. Pharm. 221 2001 143 152 (Pubitemid 32524042)
122. M.K. Reddy, and V. Labhasetwar Nanoparticle-mediated delivery of superoxide dismutase to the bra an effective strategy to reduce ischemia-reperfusion injury FASEB J. 23 2009 1384 1395
123. S. Yang Formulating protein therapeutics into particulate forms Expert Opin. Drug Deliv. 6 2009 1123 1133
124. S.C. Steiniger Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles Int. J. Cancer 109 2004 759 767 (Pubitemid 38405625)
125. T. Hekmatara Efficient systemic therapy of rat glioblastoma by nanoparticle- bound doxorubicin is due to antiangiogenic effects Clin. Neuropathol. 28 2009 153 164
126. A. Ambruosi Influence of surfactants, polymer and doxorubicin loading on the anti-tumour effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model J. Microencapsul. 23 2006 582 592 (Pubitemid 44446597)
127. J. Kreuter, and S. Gelperina Use of nanoparticles for cerebral cancer Tumori 94 2008 271 277 (Pubitemid 351838835)
128. S. Wohlfart Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers PLoS One 6 2011 e19121
129. S. Wohlfart Treatment of glioblastoma with poly(isohexyl cyanoacrylate) nanoparticles Int. J. Pharm. 2011 10.1016/j.ijpharm.2011.05.046
130. C.X. Wang Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model Brain Res. 1261 2009 91 99
131. E. Pereverzeva Intravenous tolerance of a nanoparticle-based formulation of doxorubicin in healthy rats Toxicol. Lett. 178 2008 9 19
132. S.E. Gelperina Toxicological studies of doxorubicin bound to polysorbate-80 coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma Toxicol. Lett. 126 2002 131 141 (Pubitemid 34075270)
133. H. Xin Enhanced anti-glioblastoma efficacy by PTX-loaded PEGyilated poly(e-caprolactone) nanoparticles: in vitro and in vivo evaluation Int. J. Pharm. 402 2010 238 247
134. W. Lu Aclarubicin-loaded cationic albumin conjugated pegylated nanoparticle for glioma chemotherapy in rats Int. J. Cancer 120 2007 420 431 (Pubitemid 44956856)
135. Z. Pang Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin Bioconj. Chem. 22 2011 1171 1180
136. Z. Pang Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats Mol. Pharm. 7 2010 1995 2005
137. V. Lukyanenko Therapeutic nano-object delivery to subdomains of cardiac myocytes V. Weissig, G.M. D'Souza, Organelle-Specific Pharmaceutical Nanotechnology 2010 Wiley 423 447
138. W. Jiskoot Immunological risk of injectable drug delivery systems Pharm. Res. 26 2009 1303 1314
139. W. Ulbrich, and A. Lamprecht Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammatory diseases J. R. Soc. Interface 7 2010 55 66
140. M.T. Peracchia Visualization of in vitro protein-rejecting properties of PEGylated stealth polycyanoacrylate nanoparticles Biomaterials 20 1999 1269 1275 (Pubitemid 29281378)
141. V.C.F. Mosqueira Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules Biomaterials 22 2001 2967 2979 (Pubitemid 32768704)
142. K. Knop Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives Angew. Chem. Int. Ed. Eng. 49 2010 6288 6308
143. L. Costantino Colloidal systems for CNS drug delivery Prog. Brain Res. 180 2009 35 69
144. C. Vauthier Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications Adv. Drug Deliv. Rev. 55 2003 519 548 (Pubitemid 36423302)
145. B. Semete In vivo evaluation of the biodistribution and safety of PLGA nanpoparticles as drug delivery systems Nanomedicine, NBM 6 2010 662 671
146. R. Fernandez-Urrsuno Evaluation of liver toxicological effects induced by polyalkylcyanoacrylate nanoparticles Toxicol. Appl. Pharmacol. 130 1995 272 279
147. R. Fernandez-Urrsuno Evaluation of hepatic antioxidant systems after intravenous administration of polymeric nanoparticles Biomaterials 18 1997 511 517
148. T.G. Iversen Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies Nano Today 6 2011 176 185
149. A.V. Vergoni Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution Nanomedicine, NBM 5 2009 369 377
150. M.E. Davis Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles Nature 464 2010 1067 1070
151. V. Brower RNA interference advances to early stage clinical trials J. Natl. Cancer Inst. 102 2010 1459 1461
152. Q. Zhou A randomized multicenter Phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients with unresected hepatocellular carcinoma Nanomedicine 5 2009 419 423
153. Y.L. Hu, and J.Q. Gao Potential neurotoxicity of nanoparticles Int. J. Pharm. 394 2010 115 121
154. Y. Arima Complement activation by polymers carrying dihydroxyl groups ACS Appl. Mater. Interfaces 1 2009 2400 2407
155. M.G. Stanton, and S.L. Colletti Medicinal chemistry of siRNA delivery J. Med. Chem. 53 2011 7887 7901
156. X. Yuan Recent advances of siRNA delivery by nanoparticles Expert Opin. Drug. Deliv. 8 2011 521 536
157. C. Thery Exosomes: composition, biogenesis and function Nat. Rev. Immunol. 2 2002 569 579 (Pubitemid 37328732)
158. L. Alvarez-Erviti Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes Nat. Biotechnol. 29 2011 341 345
159. S.I. van Kasteren Glyconanoparticles allow pre-symptomatic in vivo imaging of brain disease Proc. Natl. Acad. Sci. U. S. A. 106 2009 18 23
160. E.J. Kwon Targeted nonviral delivery vehicles to neural progenitor cells in the mouse subventricolar zone Biomaterials 31 2010 2417 2424
161. Y. Xiang Chloride channel-mediated brain glioma targeting of chlorotoxin-modified doxorubicine-loaded liposomes J. Control. Rel. 152 2011 402 410
162. G. Huile A cascade targeting strategy for brain neuroglial cells employing nanoparticles modified with angiopep-2 peptide and EGFP-EGF1 protein Biomaterials 32 2011 8669 8675