Abstract
The major challenge for the treatment of neuronal diseases is the inability of therapeutic moieties to cross the blood–brain barrier (BBB) and nasal mucosal barrier. The therapeutic moieties for the treatment of brain diseases lack targeting due to its non-specificity toward receptors located at BBB and Pgp efflux mechanism. This results in impeding its ability to reach to maximum effective concentration. Many of these therapeutic moieties possess dose-limiting systemic side effects which along with complex dosage regimens hinder patient compliance and result in discontinuation of treatment. A number of drug delivery and drug-targeting systems have been investigated to increase drug bioavailability and the fraction of the drug accumulated in the targeted area, in order to minimize drug degradation and loss, as well as to reduce harmful side effects. Among all, PLGA NPs have been achieved fascinating properties as a carrier system owing to its biodegradable, biocompatible, and easy functionalization properties. Most importantly PLGA is available in various ratios which can be helpful for tuning the entrapment/loading of therapeutic moieties in NPs. Intranasal delivery has come to the forefront as a method that can bypass the BBB and target drugs directly to the brain as an alternative to invasive methods. The objective of this chapter is to provide a broad overview on current strategies for brain drug delivery and its applications. It is hoped that this chapter could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB and intranasal route in both healthy and pathological conditions, this chapter revisits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Furthermore, in this chapter, various conjugation strategies for attaching targeting moieties to the surface of nanocarrier have been included. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using noninvasive techniques to enhance brain drug uptake.
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References
Neurologic diseases [Internet]. Retrieved August 24, 2018, from https://medlineplus.gov/neurologicdiseases.html
WHO What are neurological disorders? [Internet]. WHO. Retrieved August 24, 2018, from http://www.who.int/features/qa/55/en/
Ferri, C. P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., et al. (2005). Global prevalence of dementia: A Delphi consensus study. Lancet (London, England), 366(9503), 2112–2117.
Singh, S. K., Srivastav, S., Yadav, A. K., Srikrishna, S., & Perry, G. (2016). Overview of Alzheimer’s disease and some therapeutic approaches targeting Aβ by using several synthetic and herbal compounds. Oxidative Medicine and Cellular Longevity [Internet], 2016. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807045/
Cummings, J. L., Vinters, H. V., Cole, G. M., & Khachaturian, Z. S. (1998). Alzheimer’s disease: Etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology, 51(1 Suppl 1), S2–17; discussion S65–67.
Wolters E. C. (2009). Non-motor extranigral signs and symptoms in Parkinson’s disease. Parkinsonism & Related Disorders, 15(Suppl 3):S6–S12.
Obeso, J. A., RodrĂguez-Oroz, M. C., Benitez-Temino, B., Blesa, F. J., Guridi, J., Marin, C., et al. (2008). Functional organization of the basal ganglia: Therapeutic implications for Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 23(Suppl 3), S548–S559.
Obeso, J. A., Rodriguez-Oroz, M. C., Goetz, C. G., Marin, C., Kordower, J. H., Rodriguez, M., et al. (2010). Missing pieces in the Parkinson’s disease puzzle. Nature Medicine, 16(6), 653–661.
Ho, S. C., Woo, J., & Lee, C. M. (1989). Epidemiologic study of Parkinson’s disease in Hong Kong. Neurology, 39(10), 1314–1318.
Braak, H., Rüb, U., Gai, W. P., & Del Tredici, K. (2003). Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. Journal of Neural Transmission (Vienna, Austria: 1996), 110(5), 517–536.
Schapira, A. H. V. (2005). Present and future drug treatment for Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 76(11), 1472–1478.
Factor, S. A. (2008). Current status of symptomatic medical therapy in Parkinson’s disease. Neurotherapeutics, 5(2), 164–180.
Ricard, D., Idbaih, A., Ducray, F., Lahutte, M., Hoang-Xuan, K., & Delattre, J.-Y. (2012). Primary brain tumours in adults. Lancet (London, England), 379(9830), 1984–1996.
Koo, Y.-E. L., Reddy, G. R., Bhojani, M., Schneider, R., Philbert, M. A., Rehemtulla, A., et al. (2006). Brain cancer diagnosis and therapy with nanoplatforms. Advanced Drug Delivery Reviews, 58(14), 1556–1577.
Lewandowsky, M. (1909). Zur Lehre der Cerebrospinalflussigkeit. Zeitschrift für Klinische Medizin, 40, 480–494.
Cardoso, F. L., Brites, D., & Brito, M. A. (2010). Looking at the blood-brain barrier: Molecular anatomy and possible investigation approaches. Brain Research Reviews, 64(2), 328–363.
Tapeinos, C., Battaglini, M., & Ciofani, G. (2017). Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. Journal of Controlled Release, 264, 306–332.
Abbott, N. J., Bundgaard, M., & Cserr, H. F. (1985). Tightness of the blood-brain barrier and evidence for brain interstitial fluid flow in the cuttlefish, Sepia officinalis. The Journal of Physiology, 368, 213–226.
Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology of Disease, 37(1), 13–25.
Cornford, E. M., & Hyman, S. (2005). Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy. NeuroRx: The Journal of the American Society for Experimental NeuroTherapeutics, 2(1), 27–43.
Dinda, S. C., & Pattnaik, G. (2013). Nanobiotechnology-based drug delivery in brain targeting. Current Pharmaceutical Biotechnology, 14(15), 1264–1274.
Thorne, R. G., Emory, C. R., Ala, T. A., & Frey, W. H. (1995). Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Research, 692(1–2), 278–282.
Shipley, M. T. (1985). Transport of molecules from nose to brain: Transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Research Bulletin, 15(2), 129–142.
Chapman, C. D., Frey, W. H., Craft, S., Danielyan, L., Hallschmid, M., Schiöth, H. B., et al. (2013). Intranasal treatment of central nervous system dysfunction in humans. Pharmaceutical Research, 30(10), 2475–2484.
Linazasoro, G., & Nanotechnologies for Neurodegenerative Diseases Study Group of the Basque Country (NANEDIS). (2008). Potential applications of nanotechnologies to Parkinson’s disease therapy. Parkinsonism & Related Disorders, 14(5), 383–392.
Ravi Kumar, M. N. (2000). Nano and microparticles as controlled drug delivery devices. Journal of Pharmacy & Pharmaceutical Sciences: A Publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 3(2), 234–258.
Jores, K., Mehnert, W., Drechsler, M., Bunjes, H., Johann, C., & Mäder, K. (2004). Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. Journal of Controlled Release: Official Journal of the Controlled Release Society, 95(2), 217–227.
Kreuter, J. (2001). Nanoparticulate systems for brain delivery of drugs. Advanced Drug Delivery Reviews, 47(1), 65–81.
Schroeder, U., Sommerfeld, P., Ulrich, S., & Sabel, B. A. (1998). Nanoparticle technology for delivery of drugs across the blood-brain barrier. Journal of Pharmaceutical Sciences, 87(11), 1305–1307.
Astete, C. E., & Sabliov, C. M. (2006). Synthesis and characterization of PLGA nanoparticles. Journal of Biomaterials Science. Polymer Edition, 17(3), 247–289.
Mohamed, F., & van der Walle, C. F. (2008). Engineering biodegradable polyester particles with specific drug targeting and drug release properties. Journal of Pharmaceutical Sciences, 97(1), 71–87.
Pillay, S., Pillay, V., Choonara, Y. E., Naidoo, D., Khan, R. A., du Toit, L. C., et al. (2009). Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain. International Journal of Pharmaceutics, 382(1–2), 277–290.
Gao, H., Yang, Z., Zhang, S., Cao, S., Shen, S., Pang, Z., et al. (2013). Ligand modified nanoparticles increases cell uptake, alters endocytosis and elevates glioma distribution and internalization. Scientific Reports, 3, 2534.
Gao, H., Pang, Z., & Jiang, X. (2013). Targeted delivery of nano-therapeutics for major disorders of the central nervous system. Pharmaceutical Research, 30(10), 2485–2498.
Gao, H. (2017). Perspectives on dual targeting delivery systems for brain tumors. Journal of Neuroimmune Pharmacology, 12(1), 6–16.
Du, J., Lu, W.-L., Ying, X., Liu, Y., Du, P., Tian, W., et al. (2009). Dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood-brain barrier and survival of brain tumor-bearing animals. Molecular Pharmaceutics, 6(3), 905–917.
Yin, T., Yang, L., Liu, Y., Zhou, X., Sun, J., & Liu, J. (2015). Sialic acid (SA)-modified selenium nanoparticles coated with a high blood-brain barrier permeability peptide-B6 peptide for potential use in Alzheimer’s disease. Acta Biomaterialia, 25, 172–183.
Zhang, C., Zheng, X., Wan, X., Shao, X., Liu, Q., Zhang, Z., et al. (2014). The potential use of H102 peptide-loaded dual-functional nanoparticles in the treatment of Alzheimer’s disease. Journal of Controlled Release: Official Journal of the Controlled Release Society, 192, 317–324.
Sengupta, S., Eavarone, D., Capila, I., Zhao, G., Watson, N., Kiziltepe, T., et al. (2005). Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature, 436(7050), 568–572.
Gao, H., Xiong, Y., Zhang, S., Yang, Z., Cao, S., & Jiang, X. (2014). RGD and interleukin-13 peptide functionalized nanoparticles for enhanced glioblastoma cells and neovasculature dual targeting delivery and elevated tumor penetration. Molecular Pharmaceutics, 11(3), 1042–1052.
Ruan, S., Cao, X., Cun, X., Hu, G., Zhou, Y., Zhang, Y., et al. (2015). Matrix metalloproteinase-sensitive size-shrinkable nanoparticles for deep tumor penetration and pH triggered doxorubicin release. Biomaterials, 60, 100–110.
Sharon, N., & Lis, H. (2004). History of lectins: From hemagglutinins to biological recognition molecules. Glycobiology, 14(11), 53R–62R.
Bies, C., Lehr, C.-M., & Woodley, J. F. (2004). Lectin-mediated drug targeting: History and applications. Advanced Drug Delivery Reviews, 56(4), 425–435.
Kennedy, J. F., Palva, P. M. G., Corella, M. T. S., Cavalcanti, M. S. M., & Coelho, L. C. B. B. (1995). Lectins, versatile proteins of recognition: A review. Carbohydrate Polymers, 26(3), 219–230.
Ni, Y., & Tizard, I. (1996). Lectin-carbohydrate interaction in the immune system. Veterinary Immunology and Immunopathology, 55(1–3), 205–223.
Wen, Z., Yan, Z., Hu, K., Pang, Z., Cheng, X., Guo, L., et al. (2011). Odorranalectin-conjugated nanoparticles: Preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. Journal of Controlled Release: Official Journal of the Controlled Release Society, 151(2), 131–138.
Bechara, C., & Sagan, S. (2013). Cell-penetrating peptides: 20 years later, where do we stand? FEBS Letters, 587(12), 1693–1702.
Trabulo, S., Cardoso, A. L., Mano, M., & de Lima, M. C. P. (2010). Cell-penetrating peptides—Mechanisms of cellular uptake and generation of delivery systems. Pharmaceuticals, 3(4), 961–993.
Bolhassani, A., Jafarzade, B. S., & Mardani, G. (2017). In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides. Peptides, 87, 50–63.
Rao, K. S., Reddy, M. K., Horning, J. L., & Labhasetwar, V. (2008). TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs. Biomaterials, 29(33), 4429–4438.
Liu, L., Guo, K., Lu, J., Venkatraman, S. S., Luo, D., Ng, K. C., 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(10), 1509–1517.
Suk, J. S., Suh, J., Choy, K., Lai, S. K., Fu, J., & Hanes, J. (2006). Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles. Biomaterials, 27(29), 5143–5150.
Tsui, B., Singh, V. K., Liang, J. F., & Yang, V. C. (2001). Reduced reactivity towards anti-protamine antibodies of a low molecular weight protamine analogue. Thrombosis Research, 101(5), 417–420.
Liang, J. F., Zhen, L., Chang, L.-C., & Yang, V. C. (2003). A less toxic heparin antagonist—Low molecular weight protamine. Biochemistry. Biokhimiia, 68(1), 116–120.
Xia, H., Gao, X., Gu, G., Liu, Z., Zeng, N., Hu, Q., et al. (2011). Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration. Biomaterials, 32(36), 9888–9898.
Yan, L., Wang, H., Jiang, Y., Liu, J., Wang, Z., Yang, Y., et al. (2013). Cell-penetrating peptide-modified PLGA nanoparticles for enhanced nose-to-brain macromolecular delivery. Macromolecular Research, 21(4), 435–441.
Yang, Z.-Z., Zhang, Y.-Q., Wang, Z.-Z., Wu, K., Lou, J.-N., & Qi, X.-R. (2013). Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration. International Journal of Pharmaceutics, 452(1–2), 344–354.
Kamei, N., & Takeda-Morishita, M. (2015). Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides. Journal of Controlled Release: Official Journal of the Controlled Release Society, 197, 105–110.
Lu, W., Tan, Y.-Z., Hu, K.-L., & Jiang, X.-G. (2005). Cationic albumin conjugated pegylated nanoparticle with its transcytosis ability and little toxicity against blood-brain barrier. International Journal of Pharmaceutics, 295(1–2), 247–260.
Qin, Y., Chen, H., Zhang, Q., Wang, X., Yuan, W., Kuai, R., et al. (2011). Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals. International Journal of Pharmaceutics, 420(2), 304–312.
Van Weperen, W., & Gaillard, P. (2010). Enhanced blood to brain drug delivery. Innovations in Pharmaceutical Technology, 55–57.
Patel, P. J., Acharya, N. S., & Acharya, S. R. (2013). Development and characterization of glutathione-conjugated albumin nanoparticles for improved brain delivery of hydrophilic fluorescent marker. Drug Delivery, 20(3–4), 143–155.
Smeyne, M., & Smeyne, R. J. (2013). Glutathione metabolism and Parkinson’s disease. Free Radical Biology & Medicine, 62, 13–25.
Martin, H. L., & Teismann, P. (2009). Glutathione—A review on its role and significance in Parkinson’s disease. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 23(10), 3263–3272.
Reijerkerk, A., Kooij, G., van der Pol, S. M. A., Leyen, T., Lakeman, K., van Het Hof, B., et al. (2010). The NR1 subunit of NMDA receptor regulates monocyte transmigration through the brain endothelial cell barrier. Journal of Neurochemistry, 113(2), 447–453.
Sutariya, V. (2013). Blood-brain barrier permeation of glutathione-coated nanoparticle. SOJ Pharmacy & Pharmaceutical Sciences [Internet], 1(1). Retrieved September 10, 2018, from http://symbiosisonlinepublishing.com/pharmacy-pharmaceuticalsciences/pharmacy-pharmaceuticalsciences03.php
Gaillard, P. J., Appeldoorn, C. C. M., Rip, J., Dorland, R., van der Pol, S. M. A., Kooij, G., et al. (2012). Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation. Journal of Controlled Release: Official Journal of the Controlled Release Society, 164(3), 364–369.
Nobs, L., Buchegger, F., Gurny, R., & Allémann, E. (2004). Current methods for attaching targeting ligands to liposomes and nanoparticles. Journal of Pharmaceutical Sciences, 93(8), 1980–1992.
Nicolas, J., Mura, S., Brambilla, D., Mackiewicz, N., & Couvreur, P. (2013). Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chemical Society Reviews, 42(3), 1147–1235.
Haugland, R. P., Spence, M. T. Z., Johnson, I. D., & Basey, A. (2005). The handbook: A guide to fluorescent probes and labeling technologies (10th ed.) [Internet]. Eugene, OR: Molecular Probes. Retrieved from http://lib.ugent.be/catalog/rug01:000926166
Greg, H. Bioconjugate techniques (2nd ed.) [Internet]. Retrieved September 10, 2018, from https://www.elsevier.com/books/bioconjugate-techniques/hermanson/978-0-12-370501-3
Chiu, S.-J., Ueno, N. T., & Lee, R. J. (2004). Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin) conjugated polyethylenimine. Journal of Controlled Release: Official Journal of the Controlled Release Society, 97(2), 357–369.
Werengowska-Ciećwierz, K., Wiśniewski, M., Terzyk, A. P., & Furmaniak, S. (2015). The chemistry of bioconjugation in nanoparticles-based drug delivery system [Internet]. Advances in Condensed Matter Physics. Retrieved September 10, 2018, from https://www.hindawi.com/journals/acmp/2015/198175/
Algar, W. R., Prasuhn, D. E., Stewart, M. H., Jennings, T. L., Blanco-Canosa, J. B., Dawson, P. E., et al. (2011). The controlled display of biomolecules on nanoparticles: A challenge suited to bioorthogonal chemistry. Bioconjugate Chemistry, 22(5), 825–858.
Kolb, H. C., Finn, M. G., & Sharpless, K. B. (2001). Click chemistry: Diverse chemical function from a few good reactions. Angewandte Chemie (International Ed. in English), 40(11), 2004–2021.
Hein, C. D., Liu, X.-M., & Wang, D. (2008). Click chemistry, a powerful tool for pharmaceutical sciences. Pharmaceutical Research, 25(10), 2216–2230.
Jeong, B., Bae, Y. H., Lee, D. S., & Kim, S. W. (1997). Biodegradable block copolymers as injectable drug-delivery systems. Nature, 388(6645), 860–862.
Liu, Y., Miyoshi, H., & Nakamura, M. (2007). Nanomedicine for drug delivery and imaging: A promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. International Journal of Cancer, 120(12), 2527–2537.
Mo, L., Hou, L., Guo, D., Xiao, X., Mao, P., & Yang, X. (2012). Preparation and characterization of teniposide PLGA nanoparticles and their uptake in human glioblastoma U87MG cells. International Journal of Pharmaceutics, 436(1–2), 815–824.
Zybina, A., Anshakova, A., Malinovskaya, J., Melnikov, P., Baklaushev, V., Chekhonin, V., et al. (2018). Nanoparticle-based delivery of carbamazepine: A promising approach for the treatment of refractory epilepsy. International Journal of Pharmaceutics, 547(1–2), 10–23.
Mathew, A., Fukuda, T., Nagaoka, Y., Hasumura, T., Morimoto, H., Yoshida, Y., et al. (2012). Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One, 7(3), e32616.
Salvalaio, M., Rigon, L., Belletti, D., D’Avanzo, F., Pederzoli, F., Ruozi, B., et al. (2016). Targeted polymeric nanoparticles for brain delivery of high molecular weight molecules in lysosomal storage disorders. PLoS One, 11(5), e0156452.
Hua, H., Zhang, X., Mu, H., Meng, Q., Jiang, Y., Wang, Y., et al. (2018). RVG29-modified docetaxel-loaded nanoparticles for brain-targeted glioma therapy. International Journal of Pharmaceutics, 543(1–2), 179–189.
Zaman, R. U., Mulla, N. S., Braz Gomes, K., D’Souza, C., Murnane, K. S., & D’Souza, M. J. (2018). Nanoparticle formulations that allow for sustained delivery and brain targeting of the neuropeptide oxytocin. International Journal of Pharmaceutics, 548(1), 698–706.
Cano, A., Ettcheto, M., Espina, M., Auladell, C., Calpena, A. C., Folch, J., et al. (2018). Epigallocatechin-3-gallate loaded PEGylated-PLGA nanoparticles: A new anti-seizure strategy for temporal lobe epilepsy. Nanomedicine: Nanotechnology, Biology, and Medicine, 14(4), 1073–1085.
Portioli, C., Bovi, M., Benati, D., Donini, M., Perduca, M., Romeo, A., et al. (2017). Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications: PEPTIDIC MOIETIES ENABLE BBB TRAVERSAL OF THE NPs. Journal of Biomedical Materials Research. Part A, 105(3), 847–858.
Huang, R., Han, L., Li, J., Ren, F., Ke, W., Jiang, C., et al. (2009). Neuroprotection in a 6-hydroxydopamine-lesioned Parkinson model using lactoferrin-modified nanoparticles. The Journal of Gene Medicine, 11(9), 754–763.
Kuo, Y.-C., & Tsai, H.-C. (2018). Rosmarinic acid- and curcumin-loaded polyacrylamide-cardiolipin-poly(lactide- co -glycolide) nanoparticles with conjugated 83-14 monoclonal antibody to protect β-amyloid-insulted neurons. Materials Science and Engineering: C, 91, 445–457.
Jamali, Z., Khoobi, M., Hejazi, S. M., Eivazi, N., Abdolahpour, S., Imanparast, F., et al. (2018). Evaluation of targeted curcumin (CUR) loaded PLGA nanoparticles for in vitro photodynamic therapy on human glioblastoma cell line. Photodiagnosis and Photodynamic Therapy, 23, 190–201.
Paka, G. D., & Ramassamy, C. (2017). Optimization of curcumin-loaded PEG-PLGA nanoparticles by GSH functionalization: Investigation of the internalization pathway in neuronal cells. Molecular Pharmaceutics, 14(1), 93–106.
Cui, Y., Zhang, M., Zeng, F., Jin, H., Xu, Q., & Huang, Y. (2016). Dual-targeting magnetic PLGA nanoparticles for codelivery of paclitaxel and curcumin for brain tumor therapy. ACS Applied Materials & Interfaces, 8(47), 32159–32169.
Nam, M., Lee, J., Lee, K. Y., & Kim, J. (2018). Sequential targeted delivery of liposomes to ischemic tissues by controlling blood vessel permeability. ACS Biomaterials Science & Engineering, 4(2), 532–538.
Taghizadehghalehjoughi, A., Hacimuftuoglu, A., Cetin, M., Ugur, A. B., Galateanu, B., Mezhuev, Y., et al. (2018). Effect of metformin/irinotecan-loaded poly-lactic-co-glycolic acid nanoparticles on glioblastoma: In vitro and in vivo studies. Nanomedicine, 13(13), 1595–1606.
Shin, J., Yin, Y., Park, H., Park, S., Triantafillu, U. L., Kim, Y., et al. (2018). p38 siRNA-encapsulated PLGA nanoparticles alleviate neuropathic pain behavior in rats by inhibiting microglia activation. Nanomedicine, 13(13), 1607–1621.
Ahmad, N., Ahmad, R., Alam, M., & Ahmad, F. (2018). Quantification and brain targeting of eugenol-loaded surface modified nanoparticles through intranasal route in the treatment of cerebral ischemia. Drug Research [Internet], 18. Retrieved September 10, 2018, from http://www.thieme-connect.de/DOI/DOI?10.1055/a-0596-7288
Serralheiro, A., Alves, G., Fortuna, A., & Falcão, A. (2015). Direct nose-to-brain delivery of lamotrigine following intranasal administration to mice. International Journal of Pharmaceutics, 490(1–2), 39–46.
Gartziandia, O., Egusquiaguirre, S. P., Bianco, J., Pedraz, J. L., Igartua, M., Hernandez, R. M., et al. (2016). Nanoparticle transport across in vitro olfactory cell monolayers. International Journal of Pharmaceutics, 499(1–2), 81–89.
Bonaccorso, A., Musumeci, T., Serapide, M. F., Pellitteri, R., Uchegbu, I. F., & Puglisi, G. (2017). Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization. Colloids and Surfaces. B, Biointerfaces, 154, 297–306.
Kaur, S., Manhas, P., Swami, A., Bhandari, R., Sharma, K. K., Jain, R., et al. (2018). Bioengineered PLGA-chitosan nanoparticles for brain targeted intranasal delivery of antiepileptic TRH analogues. Chemical Engineering Journal, 346, 630–639.
Abouhussein, D. M. N., Khattab, A., Bayoumi, N. A., Mahmoud, A. F., & Sakr, T. M. (2018). Brain targeted rivastigmine mucoadhesive thermosensitive in situ gel: Optimization, in vitro evaluation, radiolabeling, in vivo pharmacokinetics and biodistribution. Journal of Drug Delivery Science and Technology, 43, 129–140.
Yan, X., Xu, L., Bi, C., Duan, D., Chu, L., Yu, X., et al. (2018). Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects. International Journal of Nanomedicine, 13, 273–281.
Meng, Q., Wang, A., Hua, H., Jiang, Y., Wang, Y., Mu, H., et al. (2018). Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. International Journal of Nanomedicine, 13, 705–718.
Acknowledgment
The authors are thankful for the support from the Institute of Pharmacy, Nirma University; the CSIR, Government of India, in the form of CSIR-SRF (Grant no. 09/1048 (007)/2018 EMR-I); the Prime Minister Fellowship (SERB/PM Fellow/CII-FICCI/Meeting/2018 dated 27.02.2018); and DST-INSPIRE for providing fellowship (IF131007) as a financial assistance.
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The authors declared no conflict of interest.
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Mehta, T.A., Shah, N., Parekh, K., Dhas, N., Patel, J.K. (2019). Surface-Modified PLGA Nanoparticles for Targeted Drug Delivery to Neurons. In: Pathak, Y. (eds) Surface Modification of Nanoparticles for Targeted Drug Delivery. Springer, Cham. https://doi.org/10.1007/978-3-030-06115-9_3
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