Nanocarrier-Mediated Drug Delivery Systems for Neurodegenerative Diseases

  • Sathika G. G. Arachchige
  • Ryan Rienzie
  • Nadeesh M. AdassooriyaEmail author


The central nervous system (CNS) is affected in neurodegenerative diseases which lead to neuronal malfunction and death. The blood-brain barrier (BBB) which separates blood from the brain maintains the homeostasis in the CNS. It shows permeability only for selected substances, especially molecules which are small in size. Hence, the entry of certain drugs required for the treatment of neurodegenerative diseases is prevented. Mostly, less than 1% of drugs cross the BBB resulting in low efficiency in conventional treatment methods. The advent of nanotechnology for the treatment of neurodegenerative disease serves as a promising alternative approach. The most interesting fact is nanocarriers can be used to cross the BBB efficiently enabling them to use in targeted drug delivery. In here, drugs are combined in nanomaterials which facilitate the drug delivery across the BBB and size, type, polarity, and surface chemistry of nanoparticles are the determinants of efficacy in transporting across BBB. Nanocarriers can be designed in such a way that it does not alter the effect of the drugs. However, care has to be taken when choosing nanomaterials (NM) as some are nonbiodegradable. They can accumulate in the brain and cause toxic side effects. The fate of such particles is yet to be discovered. This chapter extensively discusses the nanocarrier-mediated drug delivery for the treatment of these diseases and their future prospects.


Central nervous system Blood-brain barrier Cell death Nanocarriers Targeted drug delivery Carrier-mediated specificity Biodegradable 



Alzheimer’s disease


Amyotrophic lateral sclerosis


Blood-brain barrier


Brain cerebrospinal fluid barrier


Convection-enhanced delivery


Central nervous system


Huntington’s disease




Lewy body dementia


Mesoporous silica NPs










Parkinson’s disease


Poly(ethylene glycol)






Polymeric nanoparticles


Short-interfering RNA


Solid lipid nanoparticles


Vascular dementia


  1. Abbasi E, Aval S, Akbarzadeh A, Milani M, Nasrabadi H, Joo S et al (2014) Dendrimers: synthesis, applications, and properties. Nanoscale Res Lett 9(1):247. Scholar
  2. Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7(1):41–53. Scholar
  3. Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE (2009) Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev 61:428. Scholar
  4. Al Khouri Fallouh N, Roblot-Treupel L, Fessi H, Devissaguet JP, Puisieux F (1986) Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules. Int J Pharm 28(2–3):125–132. Scholar
  5. Barbu E, Molnàr É, Tsibouklis J, Górecki DC (2009) The potential for nanoparticle-based drug delivery to the brain: overcoming the blood–brain barrier. Expert Opin Drug Deliv 6(6):553–565. Scholar
  6. Batrakova EV (2003) Optimal structure requirements for pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells. J Pharmacol Exp Ther 304:845. Scholar
  7. Béduneau A, Saulnier P, Benoit J-P (2007) Active targeting of brain tumors using nanocarriers. Biomaterials 28(33):4947–4967. Scholar
  8. Bezerra-Sores T, Capela JP, Elisabete M, Real Oliveira CD, Dias A, Bastos ML, Carvalho F, Lúcio M (2019) Nanocapsulated curcumin as a potential therapy for age related neurodegenerative diseases. Farmajournal 4(1):66–67Google Scholar
  9. Bharti C, Gulati N, Nagaich U, Pal A (2015) Mesoporous silica nanoparticles in target drug delivery system: a review. Int J Pharm Investig 5:124. Scholar
  10. Bhaskar S, Tian F, Stoeger T, Kreyling W, de la Fuente JM, Grazu V, Borm P, Estrada G, Ntziachristos V, Razansky D (2010) Multifunctional nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging. Part Fibre Toxicol 7:1–25.; Scholar
  11. Birrenbach G, Speiser PP (1976) Polymerized micelles and their use as adjuvants in immunology. J Pharm Sci 65:1763. Scholar
  12. Boado RJ, Tsukamoto H, Pardridge WM (1998) Drug delivery of antisense molecules to the brain for treatment of Alzheimer’s disease and cerebral AIDS. J Pharm Sci 87(11):1308–1315. Scholar
  13. Cecchelli R, Berezowski V, Lundquist S, Culot M, Renftel M, Dehouck M-P, Fenart L (2007) Modelling of the blood–brain barrier in drug discovery and development. Nat Rev Drug Discov 6(8):650–661. Scholar
  14. Chen D, Lee KH (1993) Biodistribution of calcitonin encapsulated in liposomes in mice with particular reference to the central nervous system. Biochim Biophys Acta Gen Subj 1158(3):244–250. Scholar
  15. Chen Y, Liu L (2012) Modern methods for delivery of drugs across the blood–brain barrier. Adv Drug Deliv Rev 64(7):640–665. Scholar
  16. D’Souza AA (2019) Solid lipid nanoparticles: a modern approach for the treatment of neurodegenerative diseases. In: Nanotechnology: applications in energy, drug and food. Springer, Cham, pp 209–225. Scholar
  17. D’Souza AA, Devarajan PV (2015) Asialoglycoprotein receptor mediated hepatocyte targeting - strategies and applications. J Control Release 203:126. Scholar
  18. Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ (2012) Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs 21(8):1123–1140. Scholar
  19. Das S, Carnicer-Lombarte A, Fawcett JW, Bora U (2016) Bio-inspired nano tools for neuroscience. Prog Neurobiol 142:1–22. Scholar
  20. Debinski W, Tatter SB (2009) Convection-enhanced delivery for the treatment of brain tumors. Expert Rev Neurother 9(10):1519–1527. Scholar
  21. Douroumis D, Dalal J, Patel A, Lodha A, Chaudhuri J, Edwards M, Lodha M (2012) Synthesis of mesoporous silica nanoparticles and drug loading of poorly water soluble drug cyclosporin A. J Pharm Bioallied Sci 4:92. Scholar
  22. Farokhzad OC, Langer R (2006) Nanomedicine: developing smarter therapeutic and diagnostic modalities. Adv Drug Deliv Rev 58:1456. Scholar
  23. Fenart L, Casanova A, Dehouck B, Duhem C, Slupek S, Cecchelli R, Betbeder D (1999) Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. J Pharmacol Exp Ther 291(3):1017–1022PubMedGoogle Scholar
  24. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:R1. Scholar
  25. Fornaguera C, Solans C (2016) Polymeric nanoparticles for drug delivery in neurological diseases. Curr Pathobiol Rep 4(4):189–197. Scholar
  26. Giret S, Wong Chi Man M, Carcel C (2015) Mesoporous-silica-functionalized nanoparticles for drug delivery. Chem Eur J 21(40):13850–13865. Scholar
  27. Godinho BMDC, Ogier JR, Darcy R, O’Driscoll CM, Cryan JF (2013) Self-assembling modified β-cyclodextrin nanoparticles as neuronal siRNA delivery vectors: focus on Huntington’s disease. Mol Pharm 10:640. Scholar
  28. Goyal K, Koul V, Singh Y, Anand A (2014) Targeted drug delivery to central nervous system (CNS) for the treatment of neurodegenerative disorders: trends and advances. Cent Nerv Syst Agents Med Chem 14(1):43–59. Scholar
  29. Grebowski J, Kazmierska P, Krokosz A (2013) Fullerenols as a new therapeutic approach in nanomedicine. Biomed Res Int 2013:1. Scholar
  30. Greig NH (2011) Drug delivery to the brain by blood-brain barrier circumvention and drug modification. In: Implications of the blood-brain barrier and its manipulation. Scholar
  31. Greig NH, Daly EM, Sweeney DJ, Rapoport SI (1990) Pharmacokinetics of chlorambucil-tertiary butyl ester, a lipophilic chlorambucil derivative that achieves and maintains high concentrations in brain. Cancer Chemother Pharmacol 25(5):320–325. Scholar
  32. Gupta PK, Hung CT, Perrier DG (1987) Quantitation of the release of doxorubicin from colloidal dosage forms using dynamic dialysis. J Pharm Sci 76(2):141–145. Scholar
  33. Gupta A, Eral HB, Hatton TA, Doyle PS (2016) Nanoemulsions: formation, properties and applications. Soft Matter 12(11):2826–2841. Scholar
  34. Guzman-Villanueva D, Mendiola MR, Nguyen HX, Yambao F, Yu N, Weissig V (2019) Conjugation of triphenylphosphonium cation to hydrophobic moieties to prepare mitochondria-targeting nanocarriers. In: Weissig V, Elbayoumi T (eds) Pharmaceutical nanotechnology, Methods in molecular biology, vol 2000. Humana, New York. Scholar
  35. Hadavi D, Poot AA (2016) Biomaterials for the treatment of Alzheimer’s disease. Front Bioeng Biotechnol 4.
  36. Jin H, Chen WQ, Tang XW, Chiang LY, Yang CY, Schloss JV, Wu JY (2000) Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents. J Neurosci Res 62:600.<600::AID-JNR15>3.0.CO;2-FCrossRefPubMedGoogle Scholar
  37. Kanwar J, Sriramoju B, Kanwar RK (2012) Neurological disorders and therapeutics targeted to surmount the blood–brain barrier. Int J Nanomed 7:3259. Scholar
  38. Kaur IP, Bhandari R, Bhandari S, Kakkar V (2008) Potential of solid lipid nanoparticles in brain targeting. J Control Release 127(2):97–109. Scholar
  39. Klajnert B, Bryszewska M (2001) Dendrimers: properties and applications. Review Literature and Arts of the Americas. Scholar
  40. Koo Y, Reddy G, Bhojani M, Schneider R, Philbert M, Rehemtulla A, Kopelman R (2006) Brain cancer diagnosis and therapy with nanoplatforms. Adv Drug Deliv Rev 58(14):1556–1577. Scholar
  41. Kottegoda N, Munaweera I, Madusanka N, Karunaratne V (2011) A green slow-release fertilizer composition based on urea-modified hydroxyapatite nanoparticles encapsulated wood. Curr Sci 101(1):73–78Google Scholar
  42. Kottegoda N, Sandaruwan C, Perera P, Madusanka N, Karunaratne V (2014) Modified layered nanohybrid structures for the slow release of urea. Nanosci Nanotechnol Asia 4(2):94–102. Scholar
  43. Kottegoda N, Sandaruwan C, Priyadarshana G, Siriwardhana A, Rathnayake UA, Berugoda Arachchige DM, Amaratunga GAJ (2017) Urea-hydroxyapatite nanohybrids for slow release of nitrogen. ACS Nano 11:1214. Scholar
  44. Kreuter J (2012) Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 64(Suppl):213–222. Scholar
  45. Kulkarni SA, Feng S-S (2011) Effects of surface modification on delivery efficiency of biodegradable nanoparticles across the blood–brain barrier. Nanomedicine 6(2):377–394. Scholar
  46. Lemieux P, Vinogradov SV, Gebhart CL, Guerin N, Paradis G, Nguyen HK, Kabanov AV (2000) Block and graft copolymers and nanogel (TM) copolymer networks for DNA delivery into cell. J Drug Target 8:91. Scholar
  47. Li C, Yang D, Ma P, Chen Y, Wu Y, Hou Z, Lin J (2013) Multifunctional upconversion mesoporous silica nanostructures for dual modal imaging and in vivo drug delivery. Small 9:4150. Scholar
  48. Lin C-H, Chen C-H, Lin Z-C, Fang J-Y (2017) Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. J Food Drug Anal 25(2):219–234. Scholar
  49. Linazasoro G (2008) Potential applications of nanotechnologies to Parkinson’s disease therapy. Parkinsonism Relat Disord 14:383. Scholar
  50. Lockman PR, Mumper RJ, Khan MA, Allen DD (2002) Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev Ind Pharm 28(1):1–13. Scholar
  51. Lu W (2012) Adsorptive-mediated brain delivery systems. Curr Pharm Biotechnol 13:2340. Scholar
  52. Madusanka N, de Silva KMN, Amaratunga G (2015) A curcumin activated carboxymethyl cellulose–montmorillonite clay nanocomposite having enhanced curcumin release in aqueous media. Carbohydr Polym 134:695–699. Scholar
  53. Madusanka N, Shivareddy SG, Hiralal P, Eddleston MD, Choi Y, Oliver RA, Amaratunga GA (2016) Nanocomposites of TiO2/cyanoethylated cellulose with ultra high dielectric constants. Nanotechnology 27(19):195402CrossRefGoogle Scholar
  54. Madusanka N, Sandaruwan C, Kottegoda N, Sirisena D, Munaweera I, De Alwis A, Karunaratne V, Amaratunga GA (2017) Urea–hydroxyapatite-montmorillonite nanohybrid composites as slow release nitrogen compositions. Appl Clay Sci 150:303–308CrossRefGoogle Scholar
  55. Manjunath K, Venkateswarlu V (2006) Pharmacokinetics, tissue distribution and bioavailability of nitrendipine solid lipid nanoparticles after intravenous and intraduodenal administration. J Drug Target 14:632. Scholar
  56. Martínez Á, Fuentes-Paniagua E, Baeza A, Sánchez-Nieves J, Cicuéndez M, Gõmez R et al (2015) Mesoporous silica nanoparticles decorated with carbosilane dendrons as new non-viral oligonucleotide delivery carriers. Chem Eur J 21:15651. Scholar
  57. Mathew A, Aravind A, Brahatheeswaran D, Fukuda T, Nagaoka Y, Hasumura T et al (2012) Amyloid-binding aptamer conjugated curcumin–PLGA nanoparticle for potential use in Alzheimer’s disease. Bio Nano Sci 2(2):83–93. Scholar
  58. Md S, Ali M, Baboota S, Sahni JK, Bhatnagar A, Ali J (2014) Preparation, characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting. Drug Dev Ind Pharm 40:278. Scholar
  59. Mehta AM, Sonabend AM, Bruce JN (2017) Convection-enhanced delivery. Neurotherapeutics 14(2):358–371. Scholar
  60. Milani D, Athiyah U, Hariyadi DM, Pathak YV (2019) Surface modification of nanocarriers for specific cell targeting for better therapeutic effect. In: Pathak Y (ed) Surface modification of nanoparticles for targeted drug delivery. Springer, Cham. Scholar
  61. Moghimi SM, Porter CJH, Muir IS, Illum L, Davis SS (1991) Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem Biophys Res Commun 177:861. Scholar
  62. Olivier J-C (2005) Drug transport to brain with targeted nanoparticles. NeuroRx 2(1):108–119. Scholar
  63. Orive G, Anitua E, Pedraz JL, Emerich DF (2009) Biomaterials for promoting brain protection, repair and regeneration. Nat Rev Neurosci 10(9):682–692. Scholar
  64. Pardridge WM (2001) Crossing the blood–brain barrier: are we getting it right? Drug Discov Today 6(1):1–2. Scholar
  65. Patel T, Zhou J, Piepmeier JM, Saltzman WM (2012) Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev 64(7):701–705. Scholar
  66. Polt R, Porreca F, Szabò LZ, Bilsky EJ, Davis P, Abbruscato TJ et al (1994) Glycopeptide enkephalin analogues produce analgesia in mice: evidence for penetration of the blood-brain barrier. Proc Natl Acad Sci U S A 91:7114. Scholar
  67. Poovaiah N, Davoudi Z, Peng H, Schlichtmann B, Mallapragada S, Narasimhan B, Wang Q (2018) Treatment of neurodegenerative disorders through the blood-brain barrier using nanocarriers. Nanoscale 10:16962. Scholar
  68. Popovic N, Brundin P (2006) Therapeutic potential of controlled drug delivery systems in neurodegenerative diseases. Int J Pharm 314(2):120–126. Scholar
  69. Roney C, Kulkarni P, Arora V, Antich P, Bonte F, Wu A et al (2005) Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer’s disease. J Control Release 108(2–3):193–214. Scholar
  70. Saltzman W (2001) Drug delivery: engineering principles for drug therapy. In: Drug delivery: engineering principles for drug therapy. Oxford University Press, OxfordGoogle Scholar
  71. Satarkar NS, Biswal D, Hilt JZ (2010) Hydrogel nanocomposites: a review of applications as remote controlled biomaterials. Soft Matter 6(11):2364. Scholar
  72. Schexnailder P, Schmidt G (2009) Nanocomposite polymer hydrogels. Colloid Polym Sci 287:1. Scholar
  73. Seidman S, Eckstein F, Grifman M, Soreq H (2011) Antisense technologies have a future fighting neurodegenerative diseases. Antisense Nucleic Acid Drug Dev 9:333. Scholar
  74. Shi J, Xiao Z, Kamaly N, Farokhzad OC (2011) Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation. Acc Chem Res 44:1123. Scholar
  75. Shirshahi V, Soltani M (2015) Solid silica nanoparticles: applications in molecular imaging. Contrast Media Mol Imaging 10:1. Scholar
  76. Siddiqi KS, Husen A, Sohrab SS, Yassin MO (2018) Recent status of nanomaterial fabrication and their potential applications in neurological disease management. Nanoscale Res Lett 13:231CrossRefGoogle Scholar
  77. Silva Adaya D, Aguirre-Cruz L, Guevara J, Ortiz-Islas E (2017) Nanobiomaterials’ applications in neurodegenerative diseases. J Biomater Appl 31(7):953–984. Scholar
  78. Singh LP, Bhattacharyya SK, Kumar R, Mishra G, Sharma U, Singh G, Ahalawat S (2014) Sol-gel processing of silica nanoparticles and their applications. Adv Colloid Interf Sci 214:17. Scholar
  79. Song F, Li X, Wang Q, Liao L, Zhang C (2015) Nanocomposite hydrogels and their applications in drug delivery and tissue engineering. J Biomed Nanotechnol 11(1):40–52. Scholar
  80. Songjiang Z, Lixiang W (2009) Amyloid-beta associated with chitosan nano-carrier has favorable immunogenicity and permeates the BBB. AAPS PharmSciTech 10:900. Scholar
  81. Spuch C, Navarro C (2011) Liposomes for targeted delivery of active agents against neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). J Drug Deliv 2011:1. Scholar
  82. Spuch C, Saida O, Navarro C (2012) Advances in the treatment of neurodegenerative disorders employing nanoparticles. Recent Pat Drug Deliv Formul 6(1):2–18. Scholar
  83. Suriyaprabha R, Karunakaran G, Kavitha K, Yuvakkumar R, Rajendran V, Kannan N (2014) Application of silica nanoparticles in maize to enhance fungal resistance. IET Nanobiotechnol 8:133CrossRefGoogle Scholar
  84. Tomlinson E, Burger JJ (1985) [3] Incorporation of water-soluble drugs in albumin microspheres. Methods Enzymol 112:27–43. Scholar
  85. Tosi G, Bortot B, Ruozi B, Dolcetta D, Vandelli MA, Forni F, Severini GM (2013) Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier. Curr Med Chem 999(999):1–6. Scholar
  86. Trapani A, De Giglio E, Cafagna D, Denora N, Agrimi G, Cassano T et al (2011) Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int J Pharm 419(1–2):296–307. Scholar
  87. Vinogradov S, Batrakova E, Kabanov A (1999) Poly(ethylene glycol)–polyethyleneimine NanoGelTM particles: novel drug delivery systems for antisense oligonucleotides. Colloids Surf B: Biointerfaces 16(1–4):291–304. Scholar
  88. Vinogradov SV, Bronich TK, Kabanov AV (2002) Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells. Adv Drug Deliv Rev 54(1):135–147. Scholar
  89. Vinogradov SV, Batrakova EV, Kabanov AV (2004) Nanogels for oligonucleotide delivery to the brain. Bioconjug Chem 15:50. Scholar
  90. Vinogradov SV, Zeman A, Batrakova E, Kabanov A (2005) Polyplex Nanogel formulations for drug delivery of cytotoxic nucleoside analogs. J Control Release 107(1):143–157. Scholar
  91. Vivero-Escoto JL, Slowing II, Lin VSY, Trewyn BG (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6:1952. Scholar
  92. Wang Y, Gu H (2015) Core-shell-type magnetic mesoporous silica nanocomposites for bioimaging and therapeutic agent delivery. Adv Mater 27:576. Scholar
  93. Webb M, Rebstein P, Lamson W, Bally M (2008) Liposomal drug delivery: recent patents and emerging opportunities. Recent Pat Drug Deliv Formul 1:185. Scholar
  94. Wong HL, Chattopadhyay N, Wu XY, Bendayan R (2010) Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. Adv Drug Deliv Rev 62(4–5):503–517. Scholar
  95. Yang H (2010) Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis. Pharm Res 27(9):1759–1771. Scholar
  96. Yoo J, Kim J, Seo K, Jeong Y, Lee H, Khang G (2005) Characterization of degradation behavior for PLGA in various pH condition by simple liquid chromatography method. Biomed Mater Eng 15:279–288PubMedGoogle Scholar
  97. Zhang Y, Zhi Z, Jiang T, Zhang J, Wang Z, Wang S (2010) Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release 145(3):257–263. Scholar
  98. Zolle I, Rhodes BA, Wagner HN (1970) Preparation of metabolizable radioactive human serum albumin microspheres for studies of the circulation. Int J Appl Radiat Isot 21(3):155–156. Scholar

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Authors and Affiliations

  • Sathika G. G. Arachchige
    • 1
  • Ryan Rienzie
    • 2
  • Nadeesh M. Adassooriya
    • 3
    Email author
  1. 1.Postgraduate Institute of Science, University of PeradeniyaPeradeniyaSri Lanka
  2. 2.Agribusiness Centre, Faculty of AgricultureUniversity of PeradeniyaPeradeniyaSri Lanka
  3. 3.Department of Food Science and TechnologyWayamba University of Sri Lanka, MakanduraGonawilaSri Lanka

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