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Brain-Targeted Drug Delivery with Surface-Modified Nanoparticles

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Book cover Surface Modification of Nanoparticles for Targeted Drug Delivery

Abstract

Medical treatment of CNS disorders remains unsuccessful as most of the drugs could not penetrate through the blood brain barrier (BBB). Although several strategies were developed to overcome these problems, still the treatment remains ineffective. To overcome these problems, nanomedicines which are based on noninvasive strategies are an emerging trend for brain-targeted drug delivery. The advantages of nanoparticles such as small size, lipophilicity, target specificity, and controlled delivery of drug satisfy the requisites for brain targeting. However, it suffers from opsonization and phagocytosis, which can be bypassed by surface modification of nanoparticles. The carrier/transporter-mediated transcytosis, adsorptive-mediated transcytosis, receptor-mediated transcytosis are the different mechanism followed by surface-modified nanoparticles to cross the BBB. However, nanoparticles may cause neurotoxicity due to its accumulation, oxidative stress and protein aggregation. Still nanoparticles are a promising carrier for drug targeting to the brain. The present chapter highlights the significance and recent development of drug targeting to the brain with surface-modified nanoparticles, the mechanism of transport and nanotoxicity.

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References

  1. Nearly 1 in 6 of world’s population suffers from neurological disorders—UN report. Retrieved July 10, 2018, from https://news.un.org/en/story/2007/02/210312-nearly-1-6-worlds-population-suffer-neurological-disorders-un-report

  2. Saunders, N. R., Habgood, M. D., Mollgard, K., et al. (2016). The biological significance of brain barrier mechanisms: Help or hindrance in drug delivery to the central nervous system? F1000 Research, 5, 1–15.

    Article  CAS  Google Scholar 

  3. Lu, C. T., Zhao, Y. Z., Wong, H. L., et al. (2014). Current approaches to enhance CNS delivery of drugs across the brain barriers. International Journal of Nanomedicine, 9, 2241–2257.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Selin, Y., Shellef, L., Knyazer, B., et al. (2015). Anatomy and physiology of the blood-brain barrier. Seminars in Cell and Developmental Biology, 38, 2–6.

    Article  Google Scholar 

  5. Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2008). Brain endothelial cell-cell junctions: How to “open” the blood brain barrier. Current Neuropharmacology, 6(3), 179–192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Covarrubias, L. S., Slosky, L. M., & Thompson, B. J. (2014). Transporters at CNS barrier sites: Obstacles or opportunities for drug delivery? Current Pharmaceutical Design, 20(10), 1422–1449.

    Article  CAS  Google Scholar 

  7. Chen, Y., & Liu, L. (2012). Modern methods for delivery of drugs across the blood–brain barrier. Advanced Drug Delivery Reviews, 64, 640–665.

    Article  CAS  PubMed  Google Scholar 

  8. Pardridge, W. M. (2012). Drug transport across the blood–brain barrier. Journal of Cerebral Blood Flow and Metabolism, 32(11), 1959–1972.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hersh, D. S., Wadajkar, A. S., & Roberts, N. (2016). Evolving drug delivery strategies to overcome the blood brain barrier. Current Pharmaceutical Design, 22(9), 1177–1193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen, P. Y., Yeh, C. K., Hsu, P. H., et al. (2017). Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy. Oncotarget, 8(26), 42359–42371.

    PubMed  PubMed Central  Google Scholar 

  11. Bota, D. A., Desjardins, A., Quinn, J. A., et al. (2007). Interstitial chemotherapy with biodegradable BCNU (Gliadel®) wafers in the treatment of malignant gliomas. Therapeutics and Clinical Risk Management, 3(5), 707–715.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhou, Z., Singh, R., & Souweidane, M. M. (2017). Convection-enhanced delivery for diffuse intrinsic Pontine Glioma treatment. Current Neuropharmacology, 15(1), 116–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meairs, S. (2015). Facilitation of drug transport across the blood–brain barrier with ultrasound and microbubbles. Pharmaceutics, 7(3), 275–293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Azad, A. D., Pan, J., & Connolly, L. D. (2015). Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurgical Focus, 38(3), E9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jornada, D. H., Fernandes, G. F. D. S., & Chiba, D. E. (2016). The prodrug approach: A successful tool for improving drug solubility. Molecules, 21(42), 1–31.

    Google Scholar 

  16. Desai, N. (2012). Challenges in development of nanoparticle-based therapeutics. The AAPS Journal, 14(2), 282–295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wim, H. H. D. J., & Paul, J. A. B. (2008). Drug delivery and nanoparticles: Applications and hazards. International Journal of Nanomedicine, 3(2), 133–149.

    Google Scholar 

  18. Nie, S. (2010). Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine (London), 5(4), 523–528.

    Article  Google Scholar 

  19. Lahkar, A., & Das, M. K. (2013). Surface modified polymeric nanoparticles for brain targeted delivery. Current Trends in Biotechnology and Pharmacy, 7(4), 914–931.

    CAS  Google Scholar 

  20. Choi, S. W., Kim, W. S., & Kim, J. H. (2003). Surface modification of functional nanoparticles for controlled drug delivery. Journal of Dispersion Science and Technology, 24(3–4), 475–487.

    Article  CAS  Google Scholar 

  21. Zhao, M., Zhao, M., & Fu, C. (2018). Targeted therapy of intracranial glioma model mice with curcumin nanoliposomes. International Journal of Nanomedicine, 13, 1601–1610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Aditi, J., Deshpande, P., & Pattni, B. (2018). Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma. Journal of Controlled Release, 277, 89–101.

    Article  CAS  Google Scholar 

  23. Kim, S. S., Rait, A., & Kim, E. (2015). Encapsulation of temozolomide in a tumor-targeting nanocomplex enhances anti-cancer efficacy and reduces toxicity in a mouse model of glioblastoma. Cancer Letters, 369(1), 250–258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Qu, M., Lin, Q., He, S., et al. (2018). A brain targeting functionalized liposomes of the dopamine derivative N-3, 4-bis(pivaloyloxy)-dopamine for treatment of Parkinson’s disease. Journal of Controlled Release, 277, 173–182.

    Article  CAS  PubMed  Google Scholar 

  25. Sonali, S., Singh, R. P., Singh, N., et al. (2016). Transferrin liposomes of docetaxel for brain targeted cancer applications: Formulation and brain theranostics. Drug Delivery, 23(4), 1261–1271.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, Y., Zhai, M., & Chen, Z. (2017). Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma. Drug Delivery, 24(1), 1045–1055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Reddy, Y. D., Dhachinamoorthi, D., & Chandra Sekhar, K. B. (2015). A brief review on polymeric Nanoparticles for drug delivery and targeting. Journal of Medical and Pharmaceutical Innovation, 2(7), 19–32.

    CAS  Google Scholar 

  28. Khalin, I., Alyautdin, R., Wong, T. W., et al. (2016). Brain-derived neurotrophic factor delivered to the brain using poly(lactide-co-glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury. Drug Delivery, 23(9), 3520–3528.

    Article  CAS  PubMed  Google Scholar 

  29. Calvo, P., Gouritin, B., Chacun, H., et al. (2001). Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery. Pharmaceutical Research, 18(8), 1157–1166.

    Article  CAS  PubMed  Google Scholar 

  30. Lopalco, A., Hasem, A., Denora, N., et al. (2015). Oxcarbazepine-loaded polymeric nanoparticles: Development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast. International Journal of Nanomedicine, 10, 1985–1996.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Geldenhuy, W., Wehrung, D., & Groshev, A. (2015). Brain-targeted delivery of doxorubicin using glutathione-coated nanoparticles for brain cancers. Pharmaceutical Development and Technology, 20(4), 497–506.

    Article  CAS  Google Scholar 

  32. Ahmad, N., Ahmad, R., Naqvi, A. A., et al. (2016). Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of cerebral ischemia. International Journal of Biological Macromolecules, 91, 640–655.

    Article  CAS  PubMed  Google Scholar 

  33. Blasi, P., Giovagnoli, S., Schoubben, A., et al. (2007). Solid lipid nanoparticles for targeted brain drug delivery. Advanced Drug Delivery Reviews, 59, 454–477.

    Article  CAS  PubMed  Google Scholar 

  34. Ramteke, K. H., Joshi, S. A., & Dhole, S. N. (2012). Solid lipid nanoparticle: A review. IOSR Journal of Pharmacy, 2(6), 34–44.

    Article  Google Scholar 

  35. Yang, S., Zhu, J., Lu, Y., et al. (1999). Body distribution of Camptothecin solid lipid nanoparticles after oral administration. Pharmaceutical Research, 16(5), 751–757.

    Article  CAS  PubMed  Google Scholar 

  36. Kreuter, J. (1994). Nanoparticles. In Colloidal drugs delivery systems (pp. 219–342). New York: Dekker.

    Google Scholar 

  37. Kuo, Y. C., & Cheng, S. J. (2016). Brain targeted delivery of carmustine using solid lipid nanoparticles modified with tamoxifen and lectoferrin for antitumor proliferation. International Journal of Pharmaceutics, 499(1–2), 10–19.

    Article  CAS  PubMed  Google Scholar 

  38. Neves, A. R., Queiroz, J. F., & Reis, S. (2016). Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E. Nano, 14(27), 1–11.

    Google Scholar 

  39. Gandomi, N., Varshochian, R., Atyabi, F., et al. (2017). Solid lipid nanoparticles surface modified with anti-Contactin2 or anti-Neurofascin for brain targeted delivery of medicines. Pharmaceutical Development and Technology, 22(3), 426–435.

    Article  CAS  PubMed  Google Scholar 

  40. Bruun, J., Larsen, T. B., Jølck, R. I., et al. (2015). Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood-brain barrier and glioma cells. International Journal of Nanomedicine, 10, 5995–6008.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Busquets, M. A., Espargaró, A., Sabaté, R., et al. (2015). Magnetic nanoparticles cross the blood-brain barrier: When physics rises to a challenge. Nanomaterials, 5, 2231–2248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fu, T., Kong, Q., Sheng, H., et al. (2016). Value of functionalized superparamagnetic iron oxide nanoparticles in the diagnosis and treatment of acute temporal lobe epilepsy on MRI. Neural Plasticity, 2016, 1–12.

    Google Scholar 

  43. Tsuji, A., Tamai, I. I., et al. (1999). Carrier-mediated or specialized transport of drugs across the blood-brain barrier. Advanced Drug Delivery Reviews, 36(2–3), 277–290.

    Article  CAS  PubMed  Google Scholar 

  44. Du, D., Chang, N., Sun, S., et al. (2014). The role of glucose transporters in the distribution of p-aminophenyl-α-d-mannopyranoside modified liposomes within mice brain. Journal of Controlled Release, 182, 99–110.

    Article  CAS  PubMed  Google Scholar 

  45. Vemula, S., Roder, K. E., Yang, T., et al. (2009). A functional role for sodium-dependent glucose transport across the blood-brain barrier during oxygen glucose deprivation. The Journal of Pharmacology and Experimental Therapeutics, 328(2), 487–495.

    Article  CAS  PubMed  Google Scholar 

  46. Vivo, D. C. D., Trifiletti, R. R., Jacobson, R. I., et al. (1991). Defective glucose transport across the blood-brain barrier as a cause of persistent Hypoglycorrhachia, seizures, and developmental delay. The New England Journal of Medicine, 325, 703–709.

    Article  PubMed  Google Scholar 

  47. Rautio, J., Laine, K., Gynther, M., et al. (2008). Prodrug approaches for CNS delivery. The AAPS Journal, 10(1), 92–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Xie, F., Yao, N., Qin, Y., et al. (2012). Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting. International Journal of Nanomedicine, 7, 163–175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Li, X., Qu, B., Jin, X., et al. (2013). Design, synthesis and biological evaluation for docetaxel-loaded brain targeting liposome with “lock-in” function. Journal of Drug Targeting, 22(3), 251–261.

    Article  CAS  PubMed  Google Scholar 

  50. Peng, H., Du, D., Zhang, J., et al. (2013). Liposomes modified with p-aminophenyl-α-D-mannopyranoside: A promising delivery system in targeting the brain. Therapeutic Delivery, 4(12), 1475–1477.

    Article  CAS  PubMed  Google Scholar 

  51. Niu, J., Wang, A., Ke, Z., et al. (2014). Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating. Journal of Drug Targeting, 22(8), 712–723.

    Article  CAS  PubMed  Google Scholar 

  52. Jiang, X., Xin, H., Ren, Q., et al. (2014). Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment. Biomaterials, 35(1), 518–529.

    Article  CAS  PubMed  Google Scholar 

  53. Pinho, M. J., Serrao, M. P., Gomes, P., et al. (2004). Over-expression of renal LAT1 and LAT2 and enhanced L-DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney International, 66(1), 216–226.

    Article  CAS  PubMed  Google Scholar 

  54. Wang, B., Navath, R. S., Romero, R., et al. (2009). Anti-inflammatory and anti-oxidant activity of anionic dendrimer-N-acetyl cysteine conjugates in activated microglial cells. International Journal of Pharmaceutics, 377, 159–168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kharya, P., Jain, A., Gulbake, A., et al. (2013). Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting. Journal of Nanoparticle Research, 15(11), 1–12.

    Article  CAS  Google Scholar 

  56. Fernandes, J., Ghate, M. V., Mallik, B. S., et al. (2018). Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor. International Journal of Pharmaceutics, 547(1–2), 563–571.

    Article  CAS  PubMed  Google Scholar 

  57. Vadlapudi, A. D., Vadlapatla, R. K., & Mitra, A. K. (2012). Sodium dependent multivitamin transporter (SMVT): A potential target for drug delivery. Current Drug Targets, 13(7), 994–1003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Veszelka, S., Meszaros, M., Kiss, L., et al. (2017). Biotin and glutathione targeting of solid nanoparticles to cross human brain endothelial cells. Current Pharmaceutical Design, 23(28), 4198–4205.

    Article  CAS  PubMed  Google Scholar 

  59. Michel, V., Yuan, Z., Ramsubir, S., et al. (2006). Choline transport for phospholipid synthesis. Experimental Biology and Medicine (Maywood, N.J.), 231(5), 490–504.

    Article  CAS  Google Scholar 

  60. Lockman, P. R., & Allen, D. D. (2002). The transport of choline. Drug Development and Industrial Pharmacy, 28(7), 749–771.

    Article  CAS  PubMed  Google Scholar 

  61. Li, J., Yang, H., Zhang, Y., et al. (2015). Choline derivate-modified doxorubicin loaded micelle for glioma therapy. ACS Applied Materials and Interfaces, 7(38), 21589–21601.

    Article  CAS  PubMed  Google Scholar 

  62. Gajbhiye, K. R., Gajbhiye, V., Siddiqui, I. A., et al. (2017). Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro-in vivo study. Scientific Reports, 7, 1–12.

    Article  CAS  Google Scholar 

  63. Vijay, N., & Morris, M. E. (2014). Role of monocarboxylate transporters in drug delivery to the brain. Current Pharmaceutical Design, 20(10), 1487–1498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Venishetty, V. K., Samala, R., Komuravelli, R., et al. (2013). β-Hydroxybutyric acid grafted solid lipid nanoparticles: A novel strategy to improve drug delivery to brain. Nanomedicine, 9(3), 388–397.

    Article  CAS  PubMed  Google Scholar 

  65. Kou, L., Hou, Y., Yao, Q., et al. (2017). L-carnitine-conjugated nanoparticles to promote permeation across blood-brain barrier and to target glioma cells for drug delivery via the novel organic cation/carnitine transporter OCTN2. Artificial Cells, Nanomedicine and Biotechnology, 46(7), 1–12.

    Article  CAS  Google Scholar 

  66. P-glycoprotein. Retrieved July 10, 2018, from https://en.wikipedia.org/wiki/P-glycoprotein

  67. Srivalli, K. M. R., & Lakshmi, P. K. (2012). Overview of P-glycoprotein inhibitors: A rational outlook. BJPS, 48(3), 353–367.

    CAS  Google Scholar 

  68. Malmo, J., Sandvig, A., Varum, K. M., et al. (2013). Nanoparticle mediated P-glycoprotein silencing for improved drug delivery across the blood-brain barrier: A siRNA-Chitosan approach. PLoS One, 8(1), 1–8.

    Article  CAS  Google Scholar 

  69. Hoosain, F. G., Choonara, Y. E., Tomar, L. K., et al. (2015). Bypassing P-glycoprotein drug efflux mechanisms: Possible applications in Pharmaco resistant schizophrenia therapy. BioMed Research International, 2015, 484963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tam, V. H., Sosa, C., Liu, R., et al. (2016). Nanomedicine as a non-invasive strategy for drug delivery across the blood brain barrier. International Journal of Pharmaceutics, 515(1–2), 331–342.

    Article  CAS  PubMed  Google Scholar 

  71. Pardridge, W. M. (2002). Drug and gene targeting to the brain with molecular Trojan horses. Nature Reviews. Drug Discovery, 1, 131–139.

    Article  CAS  PubMed  Google Scholar 

  72. Mae, M., & Langel, U. (2006). Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery. Current Opinion in Pharmacology, 6(5), 509–514.

    Article  CAS  PubMed  Google Scholar 

  73. Madani, F., Lindberg, S., Langel, U., et al. (2011). Mechanisms of cellular uptake of cell-penetrating peptides. Journal of Biophysics, 2011, 414729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Liu, L., Guo, K., Lu, J., et al. (2008). Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG-TAT for drug delivery across the blood-brain barrier. Biomaterials, 29, 1509–1517.

    Article  CAS  PubMed  Google Scholar 

  75. Allhenn, D., Boushehri, M. A., & Lamprecht, A. (2012). Drug delivery strategies for the treatment of malignant gliomas. International Journal of Pharmaceutics, 436, 299–310.

    Article  CAS  PubMed  Google Scholar 

  76. Yadav, M., Parle, M., Sharma, N., et al. (2017). Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: Behavioral, biochemical, neurochemical and histological alterations in mice. Drug Delivery, 24(1), 1429–1440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yusuf, M., Khan, M., Khan, R. A., et al. (2016). Polysorbate-80-coated, polymeric curcumin nanoparticles for in vivo anti-depressant activity across BBB and envisaged biomolecular mechanism of action through a proposed pharmacophore model. Journal of Microencapsulation, 33(7), 646–655.

    Article  CAS  PubMed  Google Scholar 

  78. Das, M. K., Hussain, K., & Pathak, Y. V. (2013). Brain targeted delivery of Curcumin using P80-PEG-coated poly(lactide-co-glycolide) nanoparticles. Asian Journal of Chemistry, 25, S297–S301.

    Article  CAS  Google Scholar 

  79. Sun, D., Xue, A., Zhang, B., et al. (2015). Polysorbate 80-coated PLGA nanoparticles improve the permeability of acetylpuerarin and enhance its brain-protective effects in rats. The Journal of Pharmacy and Pharmacology, 67(12), 1650–1662.

    Article  CAS  PubMed  Google Scholar 

  80. Jose, S., Sowmya, S., Cinu, T. A., et al. (2014). Surface modified PLGA nanoparticles for brain targeting of Bacoside-a. European Journal of Pharmaceutical Sciences, 63, 29–35.

    Article  CAS  PubMed  Google Scholar 

  81. Demeule, M., Currie, J. C., Bertrand, Y., et al. (2008). Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector angiopep-2. Journal of Neurochemistry, 106(4), 1534–1544.

    Article  CAS  PubMed  Google Scholar 

  82. Thomas, F. C., Taskar, K., Rudraraju, V., et al. (2009). Uptake of ANG1005, a novel Paclitaxel derivative, through the blood-brain barrier into brain and experimental brain metastases of breast cancer. Pharmaceutical Research, 26(11), 2486–2494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Xin, H., Jiang, X., Gu, J., et al. (2011). Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials, 32(18), 4293–4305.

    Article  CAS  PubMed  Google Scholar 

  84. Inagaki, O. K., Mayuzumi, H., Kato, S., et al. (2014). Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice. Oncogene, 33(1), 74–84.

    Article  CAS  Google Scholar 

  85. Liu, Y., Li, J., Shao, K., et al. (2010). A leptin derived 30-amino-acid peptide modified pegylated poly-L-lysine dendrigraft for brain targeted gene delivery. Biomaterials, 31(19), 5246–5257.

    Article  CAS  PubMed  Google Scholar 

  86. Kou, Y. C., Lin, P. I., & Wang, C. C. (2011). Targeting nevirapine delivery across human brain microvascular endothelial cells using transferrin-grafted poly(lactide-co-glycolide) nanoparticles. Nanomedicine, 6(6), 1011–1106.

    Article  CAS  Google Scholar 

  87. Hu, K., Li, J., Shen, Y., et al. (2009). Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: In vitro and in vivo evaluations. Journal of Controlled Release, 134(1), 55–61.

    Article  CAS  PubMed  Google Scholar 

  88. Carroll, R. T., Bhatia, D., Geldenhuys, W., et al. (2010). Brain-targeted delivery of tempol-loaded nanoparticles for neurological disorders. Journal of Drug Targeting, 18(9), 665–674.

    Article  CAS  PubMed  Google Scholar 

  89. Zhang, S., Wang, J., & Pan, J. (2016). Baicalin-loaded PEGylated lipid nanoparticles: Characterization, pharmacokinetics, and protective effects on acute myocardial ischemia in rats. Drug Delivery, 23(9), 3696–3703.

    Article  CAS  PubMed  Google Scholar 

  90. Ramalho, M. J., Sevin, E., Gosselet, F., et al. (2018). Receptor mediated PLGA nanoparticles for glioblastoma multiforme treatment. International Journal of Pharmaceutics, 545(1–2), 84–92.

    Article  CAS  PubMed  Google Scholar 

  91. Tang, X., Liang, Y., Zhu, Y., et al. (2015). Anti-transferrin receptor-modified amphotericin B-loaded PLA-PEG nanoparticles cure candidal meningitis and reduce drug toxicity. International Journal of Nanomedicine, 10, 6227–6241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ulbrich, K., Hekmatara, T., Herbert, E., et al. (2009). Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood–brain barrier (BBB). European Journal of Pharmaceutics and Biopharmaceutics, 71(2), 251–256.

    Article  CAS  PubMed  Google Scholar 

  93. Kuo, Y. C., & Wang, I. H. (2016). Enhanced delivery of etoposide across the blood-brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles. Journal of Drug Targeting, 24(7), 645–654.

    Article  CAS  PubMed  Google Scholar 

  94. Kaur, A., Jain, S., & Tiwary, A. K. (2008). Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation. Acta Pharmaceutica, 58(1), 61–74.

    Article  CAS  PubMed  Google Scholar 

  95. Boado, R. J., Hui, E. K. W., Lu, J. Z., et al. (2010). Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein. Journal of Biotechnology, 146(1–2), 84–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ulbrich, K., Knobloch, T., & Kreuter, J. (2011). Targeting the insulin receptor: Nanoparticles for drug delivery across the blood-brain barrier (BBB). Journal of Drug Targeting, 19(2), 125–132.

    Article  CAS  PubMed  Google Scholar 

  97. Oswald, M., Geissler, S., & Goepferich, A. (2017). Targeting the central nervous system (CNS): A review of rabies virus-targeting strategies. Molecular Pharmaceutics, 14(7), 2177–2196.

    Article  CAS  PubMed  Google Scholar 

  98. Liu, Y., Huang, R., Han, L., et al. (2009). Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles. Biomaterials, 30(25), 4195–4202.

    Article  CAS  PubMed  Google Scholar 

  99. Chen, W., Zhan, C., Gu, B., et al. (2011). Targeted brain delivery of itraconazole via RVG29 anchored nanoparticles. Journal of Drug Targeting, 19(3), 228–234.

    Article  CAS  PubMed  Google Scholar 

  100. Zou, L., Tao, Y., Payne, G., et al. (2017). Targeted delivery of nano-PTX to the brain tumor-associated macrophages. Oncotarget, 8(4), 6564–6578.

    Article  PubMed  Google Scholar 

  101. Gao, Y., Wang, Z. Y., Zhang, J., et al. (2014). RVG-peptide-linked trimethylated chitosan for delivery of siRNA to the brain. Biomacromolecules, 15(3), 1010–1018.

    Article  CAS  PubMed  Google Scholar 

  102. Gaillard, P. J., Brink, A., & de Boer, A. G. (2005). Diphtheria toxin receptor-targeted brain drug delivery. International Congress Series, 1277, 185–198.

    Article  CAS  Google Scholar 

  103. Buzzi, S., Rubboli, D., Buzzi, G., et al. (2004). CRM197 (nontoxic diphtheria toxin): Effects on advanced cancer patients. Cancer Immunology, Immunotherapy, 53(11), 1041–1048.

    Article  CAS  PubMed  Google Scholar 

  104. Tosi, G., Vilella, A., Veratti, P., et al. (2015). Exploiting bacterial pathways for BBB crossing with PLGA Nanoparticles modified with a mutated form of diphtheria toxin (CRM197): In Vivo experiments. Molecular Pharmaceutics, 12(10), 3672–3684.

    Article  CAS  PubMed  Google Scholar 

  105. Hobel, S., Appeldoorn, C. C. M., Gaillard, P. J., et al. (2011). Targeted CRM197-PEG-PEI/siRNA complexes for therapeutic RNAi in Glioblastoma. Pharmaceuticals (Basel), 4(12), 1591–1606.

    Article  CAS  Google Scholar 

  106. Chen, C., Zhuji, F., JPK, J., et al. (2009). Gangliosides as high affinity receptors for tetanus neurotoxin. The Journal of Biological Chemistry, 284(39), 26569–26577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Francis JW, Bastia E, Matthews CC, et al. Tetanus toxin fragment C as a vector to enhance delivery of proteins to the CNS. Brain Research 2004; 1011(1):7-13.

    Article  CAS  PubMed  Google Scholar 

  108. Georgieva, J. V., Hoekstra, D., & Zuhorn, I. S. (2014). Smuggling drugs into the brain: An overview of Ligands targeting transcytosis for drug delivery across the blood–brain barrier. Pharmaceutics, 6(4), 557–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Stojanov, K., Georgieva, J. V., Brinkhuis, R. P., et al. (2012). In vivo biodistribution of prion- and GM1-targeted polymersomes following intravenous administration in mice. Molecular Pharmaceutics, 9(6), 1620–1627.

    Article  CAS  PubMed  Google Scholar 

  110. 5-HT receptor. Retrieved July 11, 2018, from https://en.wikipedia.org/wiki/5-HT_receptor

  111. Kuo, Y. C., & Wang, C. C. (2015). Carmustine-loaded catanionic solid lipid nanoparticles with serotonergic 1B receptor subtype antagonist for in vitro targeted delivery to inhibit brain cancer growth. Journal of Taiwan Institute of Chemical Engineers, 46, 1–14.

    Article  CAS  Google Scholar 

  112. Kuo, Y. C., & Hong, T. Y. (2014). Delivering etoposide to the brain using catanionic solid lipid nanoparticles with surface 5-HT-moduline. International Journal of Pharmaceutics, 465(1–2), 132–142.

    Article  CAS  PubMed  Google Scholar 

  113. Hansraj, G. P., Singh, S. K., & Kumar, P. (2015). Sumatriptan succinate loaded chitosan solid lipid nanoparticles for enhanced anti-migraine potential. International Journal of Biological Macromolecules, 81, 467–476.

    Article  CAS  PubMed  Google Scholar 

  114. Zhang, C., Zheng, X., & Wan, X. (2014). The potential use of H102 peptide-loaded dual-functional nanoparticles in the treatment of Alzheimer's disease. Journal of Controlled Release, 192, 317–324.

    Article  CAS  PubMed  Google Scholar 

  115. Kaluzova, M., Bouras, A., Machaidze, R., et al. (2015). Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using cetuximab-conjugated iron-oxide nanoparticles. Oncotarget, 6(11), 8788–8806.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Thomsen, L. B., Thomsen, M. S., & Moos, T. (2015). Targeted drug delivery to the brain using magnetic nanoparticles. Therapeutic Delivery, 6(10), 1145–1155.

    Article  CAS  PubMed  Google Scholar 

  117. Tian, J., Yan, C., Liu, K., et al. (2017). Paclitaxel-loaded magnetic nanoparticles: Synthesis, characterization, and application in targeting. Journal of Pharmaceutical Sciences, 106(8), 2115–2122.

    Article  CAS  PubMed  Google Scholar 

  118. Kong, S. D., Lee, J., Ramachandran, S., et al. (2012). Magnetic targeting of nanoparticles across the intact blood–brain barrier. Journal of Controlled Release, 164(1), 49–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Belhadj, Z., Zhan, C., Ying, M., et al. (2017). Multifunctional targeted liposomal drug delivery for efficient glioblastoma treatment. Oncotarget, 8(40), 66889–66900.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Dan, M., Bae, Y., Pittman, T. A., et al. (2015). Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models. Pharmaceutical Research, 32, 1615–1625.

    Article  CAS  PubMed  Google Scholar 

  121. Magnetic nano delivery of therapeutic agents across the blood brain barrier. Retrieved July 11, 2018, from http://www.florida-institute.com/comp-tech/magnetic-nanodelivery-of-therapeutic-agents-across-blood-brain-barrier

  122. Markides, H., Rotherham, M., & El Haj, A. J.. (2012). Biocompatibility and toxicity of magnetic nanoparticles in regenerative medicine. Journal of Nanomaterials, 2012, 1–12. Article ID 614094.

    Google Scholar 

  123. Song, M. M., Xu, H. L., Liang, J. X., et al. (2017). Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery. Materials Science and Engineering. C, Materials for Biological Applications, 77, 904–911.

    Article  CAS  PubMed  Google Scholar 

  124. Yan, F., Wang, Y., He, S., et al. (2013). Transferrin-conjugated, fluorescein-loaded magnetic nanoparticles for targeted delivery across the blood-brain barrier. Journal of Materials Science. Materials in Medicine, 24(10), 2371–2379.

    Article  CAS  PubMed  Google Scholar 

  125. Conroy, S., Chen F Zachary, S., et al. (2008). Tumor-targeted drug delivery and MRI contrast enhancement by chlorotoxin-conjugated iron oxide nanoparticles. Nanomedicine (London, England), 3(4), 495–505.

    Article  Google Scholar 

  126. Shevtsov, M., Nikolaev, B., Marchenko, Y., et al. (2018). Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs). International Journal of Nanomedicine, 13, 1471–1482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Shevtsov, M. A., Nikolaev, B. P., Ryzhov, V. A., et al. (2015). Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION-cmHsp70.1). Nanoscale, 7(48), 20652–20664.

    Article  CAS  PubMed  Google Scholar 

  128. Eslaminejad, T., Nematollahi-Mahani, S. N., & Ansari, M. (2017). Glioblastoma targeted gene therapy based on pEGFP/p53-loaded superparamagnetic iron oxide nanoparticles. Current Gene Therapy, 17(1), 59–69.

    Article  CAS  PubMed  Google Scholar 

  129. Ma, X., Tao, H., Yang, K., et al. (2012). A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging. Nano Research, 5(3), 199–212.

    Article  CAS  Google Scholar 

  130. Pernal, S., Wu, V. M., & Uskoković, V. (2017). Hydroxyapatite as a vehicle for the selective effect of superparamagnetic iron oxide nanoparticles against human glioblastoma cells. ACS Applied Materials and Interfaces, 9(45), 39283–39302.

    Article  CAS  PubMed  Google Scholar 

  131. Hu, Y. L., & Gao, J. Q. (2010). Potential neurotoxicity of nanoparticles. International Journal of Pharmaceutics, 394, 115–121.

    Article  CAS  PubMed  Google Scholar 

  132. Yuan, Z. Y., Hu, Y. L., & Gao, J. Q. (2015). Brain localization and neurotoxicity evaluation of Polysorbate 80-modified chitosan nanoparticles in rats. PLoS One, 10(8), 1–14.

    Google Scholar 

  133. Manke, A., Wang, L., & Rojanasakul, Y. (2013). Mechanisms of nanoparticle-induced oxidative stress and toxicity. BioMed Research International, 2013, 1–15. Article ID 942916.

    Google Scholar 

  134. Borysov, A., Krisanova, N., Chunihin, O., et al. (2014). A comparative study of neurotoxic potential of synthesized polysaccharide coated and native ferritin based magnetic nanoparticles. Croatian Medical Journal, 55, 195–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wu, J., Ding, T., & Sun, J. (2013). Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus. Neurotoxicology, 34, 243–253.

    Article  CAS  PubMed  Google Scholar 

  136. Marcato, P. D. (2008). Durán N new aspects of nanopharmaceutical delivery systems. Journal of Nanoscience and Nanotechnology, 8(5), 2216–2229.

    Article  CAS  PubMed  Google Scholar 

  137. Shwe, T. T. W., & Fujimaki, H. (2011). Nanoparticles and neurotoxicity. International Journal of Molecular Sciences, 12, 6267–6280.

    Article  CAS  Google Scholar 

  138. Tian, L., Lin, B., Wu, L., et al. (2015). Neurotoxicity induced by zinc oxide nanoparticles: Age-related differences and interaction. Scientific Reports, 5, 1–12.

    Article  CAS  Google Scholar 

  139. Zhu, X., Tian, S., & Cai, Z. (2012). Toxicity assessment of iron oxide nanoparticles in Zebrafish (Danio rerio) early life stages. PLoS One, 7(9), 1–6.

    Google Scholar 

  140. Yutong, L., Juan, L., Kaige, X., et al. (2018). Characterization of superparamagnetic iron oxide nanoparticle-induced apoptosis in PC12 cells and mouse hippocampus and striatum. Toxicology Letters, 292, 151–161.

    Article  CAS  Google Scholar 

  141. Bertolaz, N. F., Costa, C., Brandao, F., et al. (2018). Neurotoxicity assessment of oleic acid-coated iron oxide nanoparticles in SH-SY5Y cells. Toxicology, 407, 81–91.

    Article  CAS  Google Scholar 

  142. Manickam, V., Dhakshinamoorthy, V., & Perumal, E. (2018). Iron oxide Nanoparticles induces cell cycle-dependent neuronal apoptosis in mice. Journal of Molecular Neuroscience, 64(3), 352–362.

    Article  CAS  PubMed  Google Scholar 

  143. Bertolaz, N. F., Costa, C., Brandao, F., et al. (2018). Toxicological assessment of silica-coated iron oxide nanoparticles in human astrocytes. Food and Chemical Toxicology, 118, 13–23.

    Article  CAS  Google Scholar 

  144. Patel, S., Jana, S., Chetty, R., et al. (2017). Toxicity evaluation of magnetic iron oxide nanoparticles reveals neuronal loss in chicken embryo. Drug and Chemical Toxicology, 27, 1–8.

    Google Scholar 

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Acknowledgements

The authors acknowledge Department of Pharmaceutical Sciences, Dibrugarh University, Assam for their partial help with carrying out the work.

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The authors have no conflicts of interest.

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All figures and tables are original and self-made.

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  1. Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India

    Sunita Lahkar & Malay K. Das

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  1. Sunita Lahkar
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Correspondence to Malay K. Das .

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  1. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Yashwant V Pathak

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Lahkar, S., Das, M.K. (2019). Brain-Targeted Drug Delivery with Surface-Modified Nanoparticles. In: Pathak, Y. (eds) Surface Modification of Nanoparticles for Targeted Drug Delivery. Springer, Cham. https://doi.org/10.1007/978-3-030-06115-9_15

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