Skip to main content
Log in

Curcumin-loaded polymeric nanoparticles for neuroprotection in neonatal rats with hypoxic-ischemic encephalopathy

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Hypoxic-ischemic encephalopathy is the leading cause of permanent brain injury in term newborns and currently has no cure. Inflammatory processes play a key role in the progression of this disease and may be amenable to a targeted pharmaceutical intervention. Curcumin is a dietary compound with potent anti-inflammatory, antioxidant, and antiapoptotic properties but is limited in therapeutic applications due to its low aqueous solubility, low bioavailability, and rapid first-pass hepatic metabolism. To address these limitations, loading curcumin into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles may increase relevant pharmacokinetic parameters and allow for effective drug delivery to the brain. Using the Vannucci model of unilateral hypoxic-ischemic brain injury in neonatal rats, we studied the in vivo effect of curcumin-loaded PLGA-PEG nanoparticles on brain uptake and diffusion of curcumin and on neuroprotection. The curcumin-loaded nanoparticles were able to overcome the impaired blood–brain barrier, diffuse effectively through the brain parenchyma, localize in regions of injury, and deliver a protective effect in the injured neonatal brain. The application of curcumin and PLGA-PEG nanoparticle-mediated delivery to a clinically relevant model of neonatal brain injury provides greater opportunities for clinical translation of targeted therapies for hypoxic-ischemic encephalopathy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Parikh, P.; Juul, S. E. Neuroprotective strategies in neonatal brain injury. J. Pediatr. 2018, 192, 22–32.

    Article  Google Scholar 

  2. Murray, C. J. L.; Lopez, A. D. Global mortality, disability, and the contribution of risk factors: Global burden of disease study. Lancet 1997, 349, 1436–1442.

    Article  Google Scholar 

  3. Kurinczuk, J. J.; White-Koning, M.; Badawi, N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum. Dev. 2010, 86, 329–338.

    Article  Google Scholar 

  4. Robertson, C. M. T.; Perlman, M. Follow-up of the term infant after hypoxic-ischemic encephalopathy. Paediatr. Child Health 2006, 11, 278–282.

    Google Scholar 

  5. Jacobs, S. E.; Berg, M.; Hunt, R.; Tarnow-Mordi, W. O.; Inder, T. E.; Davis, P. G. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst. Rev. 2013, CD003311.

    Google Scholar 

  6. Edwards, A. D.; Brocklehurst, P.; Gunn, A. J.; Halliday, H.; Juszczak, E.; Levene, M.; Strohm, B.; Thoresen, M.; Whitelaw, A.; Azzopardi, D. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: Synthesis and meta-analysis of trial data. BMJ 2010, 340, c363.

    Article  Google Scholar 

  7. Dingley, J.; Liu, X.; Gill, H.; Smit, E.; Sabir, H.; Tooley, J.; Chakkarapani, E.; Windsor, D.; Thoresen, M. The feasibility of using a portable xenon delivery device to permit earlier xenon ventilation with therapeutic cooling of neonates during ambulance retrieval. Anesth. Analg. 2015, 120, 1331–1336.

    Article  Google Scholar 

  8. Juul, S. E.; Comstock, B. A.; Heagerty, P. J.; Mayock, D. E.; Goodman, A. M.; Hauge, S.; Gonzalez, F.; Wu, Y. W. High-dose erythropoietin for asphyxia and encephalopathy (HEAL): A randomized controlled trial—Background, aims, and study protocol. Neonatology 2018, 113, 331–338.

    Article  Google Scholar 

  9. Pauliah, S. S.; Shankaran, S.; Wade, A.; Cady, E. B.; Thayyil, S. Therapeutic hypothermia for neonatal encephalopathy in low-and middle-income countries: A systematic review and meta-analysis. PLoS One 2013, 8, e58834.

    Article  Google Scholar 

  10. Zhang, Z. Y.; Jiang, M.; Fang, J.; Yang, M. F.; Zhang, S.; Yin, Y. X.; Li, D. W.; Mao, L. L.; Fu, X. Y.; Hou, Y. J. et al. Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood-brain barrier disruption through inhibition of inflammatory response and oxidative stress. Mol. Neurobiol. 2017, 54, 1–14.

    Article  Google Scholar 

  11. Wu, A.; Noble, E. E.; Tyagi, E.; Ying, Z.; Zhuang, Y. M.; Gomez-Pinilla, F. Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders. Biochim. Biophys. Acta 2015, 1852, 951–961.

    Article  Google Scholar 

  12. Ishrat, T.; Hoda, M. N.; Khan, M. B.; Yousuf, S.; Ahmad, M.; Khan, M. M.; Ahmad, A.; Islam, F. Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT). Eur. Neuropsychopharmacol. 2009, 19, 636–647.

    Article  Google Scholar 

  13. Pulido-Moran, M.; Moreno-Fernandez, J.; Ramirez-Tortosa, C.; Ramirez-Tortosa, M. Curcumin and health. Molecules 2016, 21, 264.

    Article  Google Scholar 

  14. Sharma, R. A.; Steward, W. P.; Gescher, A. J. Pharmacokinetics and pharmacodynamics of curcumin. In The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Advances in Experimental Medicine and Biology; Aggarwal, B. B.; Surh, Y. J.; Shishodia, S., Eds.; Springer: Boston, MA, USA, 2007; Vol. 595, pp 453–454.

    Google Scholar 

  15. Patel, T.; Zhou, J. B.; Piepmeier, J. M.; Saltzman, W. M. Polymeric nanoparticles for drug delivery to the central nervous system. Adv. Drug Deliv. Rev. 2012, 64, 701–705.

    Article  Google Scholar 

  16. Kreuter, J. Nanoparticulate systems for brain delivery of drugs. Adv. Drug Deliv. Rev. 2001, 47, 65–81.

    Article  Google Scholar 

  17. Gelperina, S.; Maksimenko, O.; Khalansky, A.; Vanchugova, L.; Shipulo, E.; Abbasova, K.; Berdiev, R.; Wohlfart, S.; Chepurnova, N.; Kreuter, J. Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: Influence of the formulation parameters. Eur. J. Pharm. Biopharm. 2010, 74, 157–163.

    Article  Google Scholar 

  18. Huang, N.; Lu, S.; Liu, X. G.; Zhu, J.; Wang, Y. J.; Liu, R. T. PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering Aβ generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer’s disease mice. Oncotarget 2017, 8, 81001–81013.

    Google Scholar 

  19. Sathya, S.; Shanmuganathan, B.; Saranya, S.; Vaidevi, S.; Ruckmani, K.; Devi, K. P. Phytol-loaded PLGA nanoparticle as a modulator of Alzheimer's toxic Aβ peptide aggregation and fibrillation associated with impaired neuronal cell function. Artif. Cells Nanomed. Biotechnol., in press, DOI: 10.1080/21691401.2017.1391822.

  20. Sánchez-López, E.; Egea, M. A.; Davis, B. M.; Guo, L.; Espina M.; Silva, A. M.; Calpena, A. C.; Souto, E. M. B.; Ravindran, N.; Ettcheto, M. et al. Memantine-loaded PEGylated biodegradable nanoparticles for the treatment of glaucoma. Small 2018, 14,1701808.

    Google Scholar 

  21. Ruozi, B.; Belletti, D.; Sharma, H. S.; Sharma, A.; Muresanu, D. F.; Mössler, H.; Forni, F.; Vandelli, M. A.; Tosi, G. PLGA nanoparticles loaded cerebrolysin: Studies on their preparation and investigation of the effect of storage and serum stability with reference to traumatic brain injury. Mol. Neurobiol. 2015, 52, 899–912.

    Article  Google Scholar 

  22. Dende, C.; Meena, J.; Nagarajan, P.; Nagaraj, V. A.; Panda, A. K.; Padmanaban, G. Nanocurcumin is superior to native curcumin in preventing degenerative changes in experimental cerebral malaria. Sci. Rep. 2017, 7, 10062.

    Article  Google Scholar 

  23. Langert, K. A.; Goshu, B.; Stubbs, E. B., Jr. Attenuation of experimental autoimmune neuritis with locally administered lovastatin-encapsulating poly(lactic-co-glycolic) acid nanoparticles. J. Neurochem. 2017, 140, 334–346.

    Google Scholar 

  24. Tang, J.; Li, J. M.; Li, G.; Zhang, H. T.; Wang, L.; Li, D.; Ding, J. S. Spermidine-mediated poly(lactic-co-glycolic acid) nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis. Int. J. Nanomedicine 2017, 12, 6687–6704.

    Article  Google Scholar 

  25. Cai, Q.; Wang, L.; Deng, G.; Liu, J. H.; Chen, Q. X.; Chen, Z. B. Systemic delivery to central nervous system by engineered PLGA nanoparticles. Am. J. Transl. Res. 2016, 8, 749–764.

    Google Scholar 

  26. Nance, E. A.; Woodworth, G. F.; Sailor, K. A.; Shih, T. Y.; Xu, Q. G.; Swaminathan, G.; Xiang, D.; Eberhart, C.; Hanes, J. A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci. Transl. Med. 2012, 4, 149ra119.

    Article  Google Scholar 

  27. Suk, J. S.; Xu, Q. G.; Kim, N.; Hanes, J.; Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 2016, 99, 28–51.

    Article  Google Scholar 

  28. Mehvar, R. Modulation of the pharmacokinetics and pharmacodynamics of proteins by polyethylene glycol conjugation. J. Pharm. Pharm. Sci. 2000, 3, 125–136.

    Google Scholar 

  29. Gref, R.; Minamitake, Y.; Peracchia, M.; Trubetskoy, V.; Torchilin, V.; Langer, R. Biodegradable long-circulating polymeric nanospheres. Science 1994, 263, 1600–1603.

    Article  Google Scholar 

  30. Yallapu, M. M.; Nagesh, P. K. B.; Jaggi, M.; Chauhan, S. C. Therapeutic applications of curcumin nanoformulations. AAPS J. 2015, 17, 1341–1356.

    Article  Google Scholar 

  31. Mathew, A.; Fukuda, T.; Nagaoka, Y.; Hasumura, T.; Morimoto, H.; Yoshida, Y.; Maekawa, T.; Venugopal, K.; Kumar, D. S. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One 2012, 7, e32616.

    Article  Google Scholar 

  32. Ray, B.; Bisht, S.; Maitra, A.; Maitra, A.; Lahiri, D. K. Neuroprotective and neurorescue effects of a novel polymeric nanoparticle formulation of curcumin (NanoCurc) in the neuronal cell culture and animal model: Implications for Alzheimer’s disease. J. Alzheimers Dis. 2011, 23, 61–77.

    Article  Google Scholar 

  33. Ahmad, N.; Ahmad, I.; Umar, S.; Iqbal, Z.; Samim, M.; Ahmad, F. J. PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC/ESI-Q-ToFMS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model. Drug Deliv. 2016, 23, 2095–2114.

    Article  Google Scholar 

  34. Orunoğlu, M.; Kaffashi, A.; Pehlivan, S. B.; Şahin, S.; Söylemezoğlu, F.; Oğuz, K. K.; Mut, M. Effects of curcumin-loaded PLGA nanoparticles on the RG2 rat glioma model. Mater. Sci. Eng. C 2017, 78, 32–38.

    Article  Google Scholar 

  35. Zhang, X. M.; Li, X. J.; Hua, H. C.; Wang, A. P.; Liu, W. H.; Li, Y. X.; Fu, F. H.; Shi, Y.; Sun, K. Cyclic hexapeptideconjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue. Int. J. Nanomedicine 2017, 12, 5717–5732.

    Article  Google Scholar 

  36. Huang, H. C.; Xu, K.; Jiang, Z. F. Curcumin-mediated neuroprotection against amyloid-β-induced mitochondrial dysfunction involves the inhibition of GSK-3β. J. Alzheimers Dis. 2012, 32, 981–996.

    Article  Google Scholar 

  37. McDonald, J. W.; Johnston, M. V. Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res. Rev. 1990, 15, 41–70.

    Article  Google Scholar 

  38. Kole, A. J.; Annis, R. P.; Deshmukh, M. Mature neurons: Equipped for survival. Cell Death Dis. 2013, 4, e689.

    Article  Google Scholar 

  39. Xu, Q. G.; Boylan, N. J.; Cai, S. T.; Miao, B. L.; Patel, H.; Hanes, J. Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus. J. Control. Release 2013, 170, 279–286.

    Article  Google Scholar 

  40. Natarajan, R.; Northrop, N.; Yamamoto, B. Fluorescein isothiocyanate (FITC)-dextran extravasation as a measure of blood-brain barrier permeability. Curr. Protoc. Neurosci. 2017, 79, 9.58.1–9.58.15.

    Article  Google Scholar 

  41. Kellert, B. A.; McPherson, R. J.; Juul, S. E. A comparison of high-dose recombinant erythropoietin treatment regimens in brain-injured neonatal rats. Pediatr. Res. 2007, 61, 451–455.

    Article  Google Scholar 

  42. Zhang, F.; Nance, E.; Alnasser, Y.; Kannan, R.; Kannan, S. Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation. J. Neuroinflammation 2016, 13, 65.

    Article  Google Scholar 

  43. Nance, E.; Timbie, K.; Miller, G. W.; Song, J.; Louttit, C.; Klibanov, A. L.; Shih, T.-Y.; Swaminathan, G.; Tamargo, R. J.; Woodworth, G. F. et al. Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood-brain barrier using MRI-guided focused ultrasound. J. Control. Release 2014, 189, 123–132.

    Article  Google Scholar 

  44. Nance, E.; Zhang, C.; Shih, T.-Y.; Xu, Q. G.; Schuster, B. S.; Hanes, J. Brain-penetrating nanoparticles improve paclitaxel efficacy in malignant glioma following local administration. ACS Nano 2014, 8, 10655–10664.

    Article  Google Scholar 

  45. Nance, E.; Porambo, M.; Zhang, F.; Mishra, M. K.; Buelow, M.; Getzenberg, R.; Johnston, M.; Kannan, R. M.; Fatemi, A.; Kannan, S. Systemic dendrimer-drug treatment of ischemia-induced neonatal white matter injury. J. Control. Release 2015, 214, 112–120.

    Article  Google Scholar 

  46. Nance, E.; Zhang, F.; Mishra, M. K.; Zhang, Z.; Kambhampati, S. P.; Kannan, R. M.; Kannan, S. Nanoscale effects in dendrimer-mediated targeting of neuroinflammation. Biomaterials 2016, 101, 96–107.

    Article  Google Scholar 

  47. Juul, S. E.; Beyer, R. P.; Bammler, T. K.; McPherson, R. J.; Wilkerson, J.; Farin, F. M. Microarray analysis of high-dose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus. Pediatr. Res. 2009, 65, 485–492.

    Article  Google Scholar 

  48. Sabir, H.; Scull-Brown, E.; Liu, X.; Thoresen, M. Immediate hypothermia is not neuroprotective after severe hypoxia ischemia and is deleterious when delayed by 12 hours in neonatal rats. Stroke 2012, 43, 3364–33670.

    Article  Google Scholar 

  49. Thoresen, M.; Bågenholm, R.; Løberg, E. M.; Apricena, F.; Kjellmer, I. Posthypoxic cooling of neonatal rats provides protection against brain injury. Arch. Dis. Child. Fetal Neonatal Ed. 1996, 74, F3–F9.

    Article  Google Scholar 

  50. Thoresen, M.; Bågenholm, R.; Løberg, E. M.; Apriccna, F. The stress of being restrained reduces brain damage after a hypoxic-ischaemic insult in the 7-day-old rat. Neuroreport 1996, 7, 481–484.

    Article  Google Scholar 

  51. Pin, T. W.; Eldridge, B.; Galea, M. P. A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy. Eur. J. Paediatr. Neurol. 2009, 13, 224–234.

    Article  Google Scholar 

  52. Traudt, C. M.; McPherson, R. J.; Bauer, L. A.; Richards, T. L.; Burbacher, T. M.; McAdams, R. M.; Juul, S. E. Concurrent erythropoietin and hypothermia treatment improve outcomes in a term nonhuman primate model of perinatal asphyxia. Dev. Neurosci. 2013, 35, 491–503.

    Article  Google Scholar 

  53. Luo, J.; Borgens, R.; Shi, R. Y. Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury. J. Neurochem. 2002, 83, 471–480.

    Article  Google Scholar 

  54. Wood, T.; Osredkar, D.; Puchades, M.; Maes, E.; Falck, M.; Flatebø, T.; Walløe, L.; Sabir, H.; Thoresen, M. Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia. Sci. Rep. 2016, 6, 23430.

    Article  Google Scholar 

  55. Vannucci, R. C.; Towfighi, J.; Heitjan, D. F.; Brucklacher, R. M. Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: An experimental study in the immature rat. Pediatrics 1995, 95, 868–874.

    Google Scholar 

  56. Sabir, H.; Osredkar, D.; Maes, E.; Wood, T.; Thoresen, M. Xenon combined with therapeutic hypothermia is not neuroprotective after severe hypoxia-ischemia in neonatal rats. PLoS One 2016, 11, e0156759.

    Article  Google Scholar 

  57. Towfighi, J.; Mauger, D.; Vannucci, R. C.; Vannucci, S. J. Influence of age on the cerebral lesions in an immature rat model of cerebral hypoxia-ischemia: A light microscopic study. Dev. Brain Res. 1997, 100, 149–160.

    Article  Google Scholar 

  58. Wang, Y.; Li, S.-Y.; Shen, S.; Wang, J. Protecting neurons from cerebral ischemia/reperfusion injury via nanoparticlemediated delivery of an siRNA to inhibit microglial neurotoxicity. Biomaterials 2018, 161, 95–105.

    Article  Google Scholar 

  59. Ishii, T.; Fukuta, T.; Agato, Y.; Oyama, D.; Yasuda, N.; Shimizu, K.; Kawaguchi, A. T.; Asai, T.; Oku, N. Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced. Biochem. Biophys. Res. Commun. 2013, 430, 1201–1205.

    Article  Google Scholar 

  60. Ambruosi, A.; Gelperina, S.; Khalansky, A.; Tanski, S.; Theisen, A.; Kreuter, J. Influence of surfactants, polymer and doxorubicin loading on the anti-tumour effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model. J. Microencapsul. 2006, 23, 582–592.

    Article  Google Scholar 

  61. Ambruosi, A.; Khalansky, A. S.; Yamamoto, H.; Gelperina, S. E.; Begley, D. J.; Kreuter, J. Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastomabearing rats. J. Drug Target. 2006, 14, 97–105.

    Article  Google Scholar 

  62. Kulkarni, S. A.; Feng, S. S. Effects of surface modification on delivery efficiency of biodegradable nanoparticles across the blood-brain barrier. Nanomedicine 2011, 6, 377–394.

    Article  Google Scholar 

  63. Na, J. H.; Koo, H.; Lee, S.; Min, K. H.; Park, K.; Yoo, H.; Lee, S. H.; Park, J. H.; Kwon, I. C.; Jeong, S. et al. Real-time and non-invasive optical imaging of tumor-targeting glycol chitosan nanoparticles in various tumor models. Biomaterials 2011, 32, 5252–5261.

    Article  Google Scholar 

  64. Gref, R.; Lück, M.; Quellec, P.; Marchand, M.; Dellacherie, E.; Harnisch, S.; Blunk, T.; Müller, R.H. “Stealth” corona-core nanoparticles surface modified by polyethylene glycol (PEG): Influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf. B: Biointerfaces 2000, 18, 301–313.

    Google Scholar 

  65. Stolnik, S.; Dunn, S. E.; Garnett, M. C.; Davies, M. C.; Coombes, A. G. A.; Taylor, D. C.; Irving, M. P.; Purkiss, S. C.; Tadros, T. F.; Davis, S. S. et al. Surface modification of poly(lactide-co-glycolide) nanospheres by biodegradable poly(lactide)-poly(ethylene glycol) copolymers. Pharm. Res. 1994, 11, 1800–1808.

    Article  Google Scholar 

  66. Langer, R. W. Drug delivery and targeting. Nature 1998, 392, 5–10.

    Google Scholar 

  67. Zhang, C.; Nance, E. A.; Mastorakos, P.; Chisholm, J.; Berry, S.; Eberhart, C.; Tyler, B.; Brem, H.; Suk, J. S.; Hanes, J. Convection enhanced delivery of cisplatin-loaded brain penetrating nanoparticles cures malignant glioma in rats. J. Control. Release 2017, 263, 112–119.

    Article  Google Scholar 

  68. Xiao, R. Z.; Zeng, Z. W.; Zhou, G. L.; Wang, J. J.; Li, F. Z.; Wang, A. M. Recent advances in PEG-PLA block copolymer nanoparticles. Int. J. Nanomedicine 2010, 5, 1057–1065.

    Google Scholar 

  69. Allison, S. D. Analysis of initial burst in PLGA microparticles. Expert Opin. Drug Deliv. 2008, 5, 615–628.

    Article  Google Scholar 

  70. Yang, C. H.; Zhang, X. J.; Fan, H. G.; Liu, Y. Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res. 2009, 1282, 133–141.

    Article  Google Scholar 

  71. Esatbeyoglu, T.; Huebbe, P.; Ernst, I. M. A.; Chin, D.; Wagner, A. E.; Rimbach, G. Curcumin-from molecule to biological function. Angew. Chem., Int. Ed. 2012, 51, 5308–5332.

    Article  Google Scholar 

  72. Lin, J. K. Molecular targets of curcumin. In The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. Advances in Experimental Medicine and Biology; Aggarwal, B. B.; Surh, Y. J.; Shishodia, S., Eds.; Springer: Boston, MA, USA, 2007; Vol. 595, pp 227–243.

    Google Scholar 

  73. Zhu, H. T.; Bian, C.; Yuan, J. C.; Chu, W. H.; Xiang, X.; Chen, F.; Wang, C. S.; Feng, H.; Lin, J. K. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury. J. Neuroinflammation 2014, 11, 59.

    Article  Google Scholar 

  74. Liu, Z. J.; Liu, W.; Liu, L.; Xiao, C.; Wang, Y.; Jiao, J. S. Curcumin protects neuron against cerebral ischemia-induced inflammation through improving PPAR-Gamma function. Evid. Based Complement. Alternat. Med. 2013, 2013, 470975.

    Google Scholar 

  75. Huang, H. C.; Chang, P.; Lu, S.-Y.; Zheng, B.-W.; Jiang, Z.-F. Protection of curcumin against amyloid-β-induced cell damage and death involves the prevention from NMDA receptor-mediated intracellular Ca2+ elevation. J. Recept. Signal Transduct. 2015, 35, 450–457.

    Article  Google Scholar 

  76. Tiwari, S. K.; Agarwal, S.; Seth, B.; Yadav, A.; Nair, S.; Bhatnagar, P.; Karmakar, M.; Kumari, M.; Chauhan, L. K. S.; Patel, D. K. et al. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer's disease model via canonical Wnt/β-catenin pathway. ACS Nano 2014, 8, 76–103.

    Article  Google Scholar 

  77. Hagberg, H.; Gressens, P.; Mallard, C. Inflammation during fetal and neonatal life: Implications for neurologic and neuropsychiatric disease in children and adults. Ann. Neurol. 2012, 71, 444–457.

    Article  Google Scholar 

  78. Vargas, D. L.; Nascimbene, C.; Krishnan, C.; Zimmerman, A. W.; Pardo, C. A. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 2005, 57, 67–81.

    Article  Google Scholar 

  79. O’Callaghan, J. P.; Sriram, K.; Miller, D. B. Defining “neuroinflammation”. Ann. N. Y. Acad. Sci. 2008, 1139, 318–330.

    Article  Google Scholar 

  80. Hassell, K. J.; Ezzati, M.; Alonso-Alconada, D.; Hausenloy, D. J.; Robertson, N. J. New horizons for newborn brain protection: Enhancing endogenous neuroprotection. Arch. Dis. Child. Fetal Neonatal Ed. 2015, 100, F541–F552.

    Article  Google Scholar 

  81. Ameruoso, A.; Palomba, R.; Palange, A. L.; Cervadoro, A.; Lee, A.; Di Mascolo, D.; Decuzzi, P. Ameliorating amyloid-β fibrils triggered inflammation via curcumin-loaded polymeric nanoconstructs. Front. Immunol. 2017, 8, 1411.

    Article  Google Scholar 

  82. Umerska, A.; Gaucher, C.; Oyarzun-Ampuero, F.; Fries-Raeth, I.; Colin, F.; Villamizar-Sarmiento, M. G.; Maincent, P.; Sapin-Minet, A. Polymeric nanoparticles for increasing oral bioavailability of curcumin. Antioxidants 2018, 7, 46.

    Article  Google Scholar 

  83. Verderio, P.; Bonetti, P.; Colombo, M.; Pandolfi, L.; Prosperi, D. Intracellular drug release from curcuminloaded PLGA nanoparticles induces G2/M block in breast cancer cells. Biomacromolecules 2013, 14, 672–682.

    Article  Google Scholar 

  84. Basniwal, R. K.; Khosla, R.; Jain, N. Improving the anticancer activity of curcumin using nanocurcumin dispersion in water. Nutr. Cancer 2014, 66, 1015–1022.

    Article  Google Scholar 

  85. Berger, H. R.; Morken, T. S.; Vettukattil, R.; Brubakk, A.-M.; Sonnewald, U.; Widerøe, M. No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat. J. Neurochem. 2016, 136, 339–350.

    Article  Google Scholar 

  86. Di Giorgio, A. M.; Hou, Y. J.; Zhao, X. R.; Zhang, B.; Lyeth, B. G.; Russell, M. J. Dimethyl sulfoxide provides neuroprotection in a traumatic brain injury model. Restor. Neurol. Neurosci. 2008, 26, 501–507.

    Google Scholar 

  87. Smith, A. L.; Garbus, H.; Rosenkrantz, T. S.; Fitch, R. H. Sex differences in behavioral outcomes following temperature modulation during induced neonatal hypoxic ischemic injury in rats. Brain Sci. 2015, 5, 220–240.

    Article  Google Scholar 

  88. Burnsed, J. C.; Chavez-Valdez, R.; Hossain, M. S.; Kesavan, K.; Martin, L. J.; Zhang, J. Y.; Northington, F. J. Hypoxiaischemia and therapeutic hypothermia in the neonatal mouse brain—A longitudinal study. PLoS One 2015, 10, e0118889.

    Article  Google Scholar 

  89. Smith, A. L.; Alexander, M.; Rosenkrantz, T. S.; Sadek, M. L.; Fitch, R. H. Sex differences in behavioral outcome following neonatal hypoxia ischemia: Insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury. Exp. Neurol. 2014, 254, 54–67.

    Article  Google Scholar 

  90. Cohen, S. S.; Stonestreet, B. S. Sex differences in behavioral outcome following neonatal hypoxia ischemia: Insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic injury. Exp. Neurol. 2014, 256, 70–73.

    Article  Google Scholar 

  91. Nie, X. J.; Lowe, D. W.; Rollins, L. G.; Bentzley, J.; Fraser, J. L.; Martin, R.; Singh, I.; Jenkins, D. Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia. Neurosci. Res. 2016, 108, 24–33.

    Article  Google Scholar 

  92. Demarest, T. G.; McCarthy, M. M. Sex differences in mitochondrial (dys)function: Implications for neuroprotection. J. Bioenerg. Biomembr. 2015, 47, 173–188.

    Article  Google Scholar 

  93. Jatana, M.; Singh, I.; Singh, A. K.; Jenkins, D. Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr. Res. 2006, 59, 684–689.

    Article  Google Scholar 

Download references

Acknowledgements

This manuscript was supported by the Burroughs Wellcome Fund Career Award at Scientific Interfaces (E. N.) and the University of Washington Department of Pediatrics Neonatal Biology Research Grant (P. P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Burroughs Wellcome Fund.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elizabeth Nance.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joseph, A., Wood, T., Chen, CC. et al. Curcumin-loaded polymeric nanoparticles for neuroprotection in neonatal rats with hypoxic-ischemic encephalopathy. Nano Res. 11, 5670–5688 (2018). https://doi.org/10.1007/s12274-018-2104-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-018-2104-y

Keywords

Navigation