Surface Functionalization of PLGA Nanoparticles to Increase Transport across the BBB for Alzheimer’s Disease
Source abstract
Abstract
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that accounts for about 60% of all diagnosed cases of dementia worldwide. Although there are currently several drugs marketed for its treatment, none are capable of slowing down or stopping the progression of AD. The role of the blood-brain barrier (BBB) plays a key role in the design of a successful treatment for this neurodegenerative disease. Nanosized particles have been proposed as suitable drug delivery systems to overcome BBB with the purpose of increasing bioavailability of drugs in the brain. Biodegradable poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) have been particularly regarded as promising drug delivery systems as they can be surface-tailored with functionalized molecules for site-specific targeting. In this review, a thorough discussion about the most recent functionalization strategies based on PLGA-NPs for AD and their mechanisms of action is provided, together with a description of AD pathogenesis and the role of the BBB in brain targeting.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Alzheimer's disease research and treatments · Advanced Drug Delivery Systems · Nanoparticle-Based Drug Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), University of Barcelona, 08028 Barcelona, Spain
Research Center and Memory Clinic, Fundació ACE. Institut Català de Neurociències Aplicades—International University of Catalunya (UIC), 08017 Barcelona, Spain
Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-458 Coimbra, Portugal
References (100+)
Show source-provided references
1. Neuropathological Alterations in Alzheimer Disease
2. Wong, K.H., Riaz, M.K., Xie, Y., Zhang, X., Liu, Q., Chen, H., Bian, Z., Chen, X., Lu, A., and Yang, Z. (2019). Review of Current Strategies for Delivering Alzheimer’s Disease Drugs across the Blood-Brain Barrier. Int. J. Mol. Sci., 20.10.3390/ijms20020381 ↗
3. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier10.2174/1381612822666151221150733 ↗
4. Nanoscale drug delivery systems and the blood–brain barrier10.2147/IJN.S52236 ↗
5. Biodegradable polymeric nanoparticles based drug delivery systems10.1016/j.colsurfb.2009.09.001 ↗
6. Nanoparticulate Systems for Drug Delivery and Targeting to the Central Nervous System10.1111/j.1755-5949.2010.00199.x ↗
7. Li, J. (2012). Surface-Modified PLGA Nanoparticles for Targeted Drug Delivery to Neurons. Surface Modification of Nanoparticles for Targeted Drug Delivery, Springer.
8. Differential receptor-mediated drug targeting to the diseased brain10.1517/17425240902806383 ↗
9. PLGA-based nanoparticles: An overview of biomedical applications10.1016/j.jconrel.2012.01.043 ↗
10. Cholinesterase inhibitors as Alzheimer’s therapeutics (Review)
11. Genetics of Alzheimer’s disease10.1177/0891988710383571 ↗
12. The incidence of dementia: A meta-analysis10.1212/WNL.51.3.728 ↗
13. Dementia and Alzheimer Disease Incidence10.1001/archneur.59.11.1737 ↗
14. Current and future treatments for Alzheimer’s disease10.1177/1756285612461679 ↗
15. Langa, K.M. (2018). Cognitive Aging, Dementia, and the Future of an Aging Population. Future Directions for the Demography of Aging, National Academies Press.
16. Drug development in Alzheimer’s disease: The path to 202510.1186/s13195-016-0207-9 ↗
17. Frequency of stages of Alzheimer-related lesions in different age categories10.1016/S0197-4580(97)00051-1 ↗
18. Visualization of Aβ42 and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ4210.1016/0896-6273(94)90458-8 ↗
19. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms10.1111/j.1471-4159.2005.03578.x ↗
20. Alzheimer’s Aβ42 and Aβ40 peptides form interlaced amyloid fibrils10.1111/jnc.12202 ↗
21. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease10.1038/349704a0 ↗
22. APP processing in Alzheimer’s disease10.1186/1756-6606-4-3 ↗
23. Alzheimer’s disease10.1111/ene.13439 ↗
24. Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure10.1038/ncomms13527 ↗
25. The Aβ Hypothesis10.1111/j.1750-3639.2005.tb00104.x ↗
26. Three dimensions of the amyloid hypothesis: Time, space and ‘wingmen’10.1038/nn.4018 ↗
27. Alzheimer’s disease hypothesis and related therapies10.1186/s40035-018-0107-y ↗
28. Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau10.1073/pnas.94.1.298 ↗
29. Tau Aggregation in Alzheimer’s Disease10.4161/pri.1.1.4055 ↗
30. Tau in Alzheimer Disease and Related Tauopathies10.2174/156720510793611592 ↗
31. Šimić, G., Leko, M.B., Wray, S., Harrington, C.R., Delalle, I., Jovanov-Milošević, N., Bažadona, D., Buée, L., De Silva, R., and Di Giovanni, G. (2016). Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules, 6.10.3390/biom6010006 ↗
32. Hyperphosphorylation of Microtubule-Associated Protein Tau: A Promising Therapeutic Target for Alzheimer Disease10.2174/092986708785909111 ↗
33. Brier, M.R., Gordon, B., Friedrichsen, K., Mccarthy, J., Stern, A., Owen, C., Aldea, P., Su, Y., Hassenstab, J., and Cairns, N.J. (2016). Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci. Transl. Med., 8.10.1126/scitranslmed.aaf2362 ↗
34. Inflammation as a central mechanism in Alzheimer’s disease10.1016/j.trci.2018.06.014 ↗
35. Optimizing phase II of drug development for disease-modifying compounds10.1016/j.jalz.2007.10.002 ↗
36. Zhang, M., Schmitt-Ulms, G., Sato, C., Xi, Z., Zhang, Y., Zhou, Y., George-Hyslop, P.S., and Rogaeva, E. (2016). Drug Repositioning for Alzheimer’s Disease Based on Systematic ‘omics’ Data Mining. PLoS ONE, 11.10.1371/journal.pone.0168812 ↗
37. Current Therapeutic Options for Alzheimers Disease10.2174/138920207783769549 ↗
38. Management of Neuropsychiatric Symptoms in People with Dementia
39. Alzheimer dementia: Starting, stopping drug therapy10.3949/ccjm.85a.16080 ↗
40. Appraising the brain’s energy budget10.1073/pnas.172399499 ↗
41. Sugar for the brain: The role of glucose in physiological and pathological brain function10.1016/j.tins.2013.07.001 ↗
42. Structure and function of the blood-brain barrier10.1016/j.nbd.2009.07.030 ↗
43. Astrocyte-endothelial interactions at the blood-brain barrier10.1038/nrn1824 ↗
44. Kandel, E.R., Schwartz, J.H., and Jessell, T.M. (2000). Principles of Neural Science, McGraw-Hill.
45. Pandit, R., Chen, L., and Götz, J. (2019). The blood-brain barrier: Physiology and strategies for drug delivery. Adv. Drug Deliv. Rev.10.1016/j.addr.2019.11.009 ↗
46. Dynamics of CNS Barriers: Evolution, Differentiation, and Modulation10.1007/s10571-004-1374-y ↗
47. Teleanu, D.M., Chircov, C., Grumezescu, A.M., Volceanov, A., and Teleanu, R.I. (2018). Blood-Brain Delivery Methods Using Nanotechnology. Pharmaceutics, 10.10.3390/pharmaceutics10040269 ↗
48. Peripheral Nerve pericytes originating from the blood-nerve barrier expresses tight junctional molecules and transporters as barrier-forming cells10.1002/jcp.21508 ↗
49. A new blood–brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes10.1016/j.neuint.2008.12.002 ↗
50. Blood-brain barrier structure and function and the challenges for CNS drug delivery10.1007/s10545-013-9608-0 ↗
51. Structure of the blood-brain barrier and its role in the transport of amino acids10.1093/jn/136.1.218S ↗
52. Daneman, R., and Prat, A. (2015). The Blood-Brain Barrier. Neuroimmune Pharmacol., 21–38.10.1101/cshperspect.a020412 ↗
53. Fine structural localization of a blood-brain barrier to exogenous peroxidase10.1083/jcb.34.1.207 ↗
54. Junctions between intimately apposed cell membranes in the vertebrate brain10.1083/jcb.40.3.648 ↗
55. Transport of proteins across normal cerebral arterioles10.1002/cne.901520103 ↗
56. Morphometric analysis of CNS microvascular endothelium10.1016/0026-2862(85)90042-1 ↗
57. Blood-brain barrier transport machineries and targeted therapy of brain diseases10.15171/bi.2016.30 ↗
58. Drug Transport across the Blood–Brain Barrier
59. Crossing the Blood–Brain Barrier: Recent Advances in Drug Delivery to the Brain10.1007/s40263-016-0405-9 ↗
60. The blood-brain barrier: Bottleneck in brain drug development10.1602/neurorx.2.1.3 ↗
61. Strategies to advance translational research into brain barriers10.1016/S1474-4422(07)70326-5 ↗
62. Delivery of therapeutic agents to the central nervous system: The problems and the possibilities10.1016/j.pharmthera.2004.08.001 ↗
63. Open questions for Alzheimer’s disease immunotherapy10.1186/alzrt233 ↗
64. The influence of drug-like concepts on decision-making in medicinal chemistry10.1038/nrd2445 ↗
65. Modulating the paracellular pathway at the blood–brain barrier: Current and future approaches for drug delivery to the CNS10.1016/j.ddtec.2016.07.008 ↗
66. Penetrating the Blood Brain Barrier: Promise of Novel Nanoplatforms and Delivery Vehicles10.1021/acsnano.5b05341 ↗
67. Preparation and In Vitro Analysis of Microcapsule Thalidomide Formulation for Targeted Suppression of TNF-α10.1080/10717540500466097 ↗
68. Nanocarriers: Promising Vehicle for Bioactive Drugs10.1248/bpb.29.1790 ↗
69. Drug Permeation across the Blood-Brain Barrier: Applications of Nanotechnology10.9734/BJMMR/2015/15493 ↗
70. Modern methods for delivery of drugs across the blood-brain barrier10.1016/j.addr.2011.11.010 ↗
71. Blood brain barrier: An overview on strategies in drug delivery, realistic in vitro modeling and in vivo live tracking10.1080/21688370.2015.1129476 ↗
72. Khalil, I.R., Burns, A.T.H., Radecka, I., Kowalczuk, M., Khalaf, T., Adamus, G., Johnston, B., and Khechara, M.P. (2017). Bacterial-Derived Polymer Poly-y-Glutamic Acid (y-PGA)-Based Micro/Nanoparticles as a Delivery System for Antimicrobials and Other Biomedical Applications. Int. J. Mol. Sci., 18.10.3390/ijms18020313 ↗
73. PLGA-Based Nanoparticles in Cancer Treatment10.3389/fphar.2018.01260 ↗
74. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines10.1186/1477-3155-9-55 ↗
75. Polymeric nanoparticles for drug delivery to the central nervous system10.1016/j.addr.2011.12.006 ↗
76. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles)10.1016/0006-8993(95)00023-J ↗
77. Polybutylcyanoacrylate nanocarriers as promising targeted drug delivery systems10.3109/1061186X.2015.1020426 ↗
78. Sulheim, E., Iversen, T.-G., Nakstad, V.T., Klinkenberg, G., Sletta, H., Schmid, R., Hatletveit, A.R., Wågbø, A.M., Sundan, A., and Skotland, T. (2017). Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles. Int. J. Mol. Sci., 18.10.3390/ijms18112454 ↗
79. Szwed, M., Sønstevold, T., Øverbye, A., Engedal, N., Grallert, B., Mørch, Ý., Iversen, T.-G., Skotland, T., Sandvig, K., and Torgersen, M.L. (2018). The alkyl side chain of PACA nanoparticles dictates the impact on cellular stress responses and the mode of particle-induced cell death. BioRxiv, 304618.10.1101/304618 ↗
80. Chitosan Nanoparticles: A Promising System in Novel Drug Delivery10.1248/cpb.58.1423 ↗
81. Mohammed, M.A., Syeda, J.T.M., Wasan, K.M., and Wasan, E.K. (2017). An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery. Pharmaceutics, 9.10.3390/pharmaceutics9040053 ↗
82. PLGA-based nanoparticles: A new paradigm in biomedical applications10.1016/j.trac.2015.06.014 ↗
83. Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates10.1016/j.ijpharm.2017.05.015 ↗
84. Synthesis, Characterization, and Study of PLGA Copolymer in Vitro Degradation10.4236/jbnb.2015.61002 ↗
85. Pandey, A., and Jain, D.S. (2015). Poly Lactic-Co-Glycolic Acid (PLGA) Copolymer and Its Pharmaceutical Application. Handbook of Polymers for Pharmaceutical Technologies, Scrivener.10.1002/9781119041412.ch6 ↗
86. Controlled Ring-Opening Polymerization of Lactide and Glycolide10.1021/cr040002s ↗
87. Review on hydrolytic degradation behavior of biodegradable polymers from controlled drug delivery system
88. Polymer degradation and drug delivery in PLGA-based drug-polymer applications: A review of experiments and theories10.1002/jbm.b.33648 ↗
89. The Preparation and Characterization of Poly(lactide-co-glycolide) Microparticles. II. The Entrapment of a Model Protein Using a (Water-in-Oil)-in-Water Emulsion Solvent Evaporation Technique10.1023/A:1018980020506 ↗
90. Controlled release from bioerodible polymers: Effect of drug type and polymer composition10.1016/j.jconrel.2004.10.019 ↗
91. Paclitaxel release from micro-porous PLGA disks10.1016/j.ces.2009.07.016 ↗
92. Biodegradable microspheres as controlled-release tetanus toxoid delivery systems10.1016/0264-410X(94)90092-2 ↗
93. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems—A review10.1016/j.ijpharm.2011.05.049 ↗
94. Recent advances in the formulation of PLGA microparticles for controlled drug delivery10.1007/s40204-020-00139-y ↗
95. Nanoparticles and nanofibers for topical drug delivery10.1016/j.jconrel.2015.10.049 ↗
96. PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: Effects of formulation parameters10.1039/C9RA10857B ↗
97. Systemic delivery to central nervous system by engineered PLGA nanoparticles
98. Concepts and practices used to develop functional PLGA-based nanoparticulate systems10.2147/IJN.S40579 ↗
99. Hoyos-Ceballos, G.P., Ruozi, B., Ottonelli, I., Da Ros, F., Vandelli, M.A., Forni, F., Daini, E., Vilella, A., Zoli, M., and Tosi, G. (2020). PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study. Pharmaceutics, 12.10.3390/pharmaceutics12010072 ↗
100. Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain10.1016/j.biomaterials.2009.09.104 ↗