Targeted Delivery of Nano-therapeutics for Major Disorders of the Central Nervous System

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2013 Jun 26

PMID 23797465

Citations 39

Authors

Huile Gao

Zhiqing Pang

Xinguo Jiang

Affiliations

Soon will be listed here.

Abstract

Major central nervous system (CNS) disorders, including brain tumors, Alzheimer’s disease, Parkinson’s disease, and stroke, are significant threats to human health. Although impressive advances in the treatment of CNS disorders have been made during the past few decades, the success rates are still moderate if not poor. The blood–brain barrier (BBB) hampers the access of systemically administered drugs to the brain. The development of nanotechnology provides powerful tools to deliver therapeutics to target sites. Anchoring them with specific ligands can endow the nano-therapeutics with the appropriate properties to circumvent the BBB. In this review, the potential nanotechnology-based targeted drug delivery strategies for different CNS disorders are described. The limitations and future directions of brain-targeted delivery systems are also discussed.

Citing Articles

Intranasal overdose reversal formulations: a rapid review of available agents.

Bernosky-Smith K, Painter O, Butler S, Patel D, Clemency B, Lynch J Pain Manag. 2025; 15(2):105-113.

PMID: 39902734 PMC: 11853544. DOI: 10.1080/17581869.2025.2461445.

Nanocarrier-mediated siRNA delivery: a new approach for the treatment of traumatic brain injury-related Alzheimer's disease.

Jin J, Zhang H, Lu Q, Tian L, Yao S, Lai F Neural Regen Res. 2024; 20(9):2538-2555.

PMID: 39314170 PMC: 11801294. DOI: 10.4103/NRR.NRR-D-24-00303.

Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Mesut B, Al-Mohaya M, Gholap A, Yesilkaya E, Das U, Akhtar M Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(12):9243-9279.

PMID: 38963550 DOI: 10.1007/s00210-024-03212-6.

A machine learning-based quantitative model (LogBB_Pred) to predict the blood-brain barrier permeability (logBB value) of drug compounds.

Shaker B, Lee J, Lee Y, Yu M, Lee H, Lee E Bioinformatics. 2023; 39(10).

PMID: 37713469 PMC: 10560102. DOI: 10.1093/bioinformatics/btad577.

Strategies for enhanced bioavailability of oxime reactivators in the central nervous system.

Prchalova E, Kohoutova Z, Knittelova K, Malinak D, Musilek K Arch Toxicol. 2023; 97(11):2839-2860.

PMID: 37642747 DOI: 10.1007/s00204-023-03587-0.

References

Song B, Vinters H, Wu D, Pardridge W . Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. J Pharmacol Exp Ther. 2002; 301(2):605-10. DOI: 10.1124/jpet.301.2.605. View

Hanson L, Roeytenberg A, Martinez P, Coppes V, Sweet D, Rao R . Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J Pharmacol Exp Ther. 2009; 330(3):679-86. PMC: 2729791. DOI: 10.1124/jpet.108.149807. View

Ren T, Xu N, Cao C, Yuan W, Yu X, Chen J . Preparation and therapeutic efficacy of polysorbate-80-coated amphotericin B/PLA-b-PEG nanoparticles. J Biomater Sci Polym Ed. 2009; 20(10):1369-80. DOI: 10.1163/092050609X12457418779185. View

Yang Z, Zhang Y, Yang Y, Sun L, Han D, Li H . Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine. 2010; 6(3):427-41. DOI: 10.1016/j.nano.2009.11.007. View

Pang Z, Gao H, Yu Y, Guo L, Chen J, Pan S . Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem. 2011; 22(6):1171-80. DOI: 10.1021/bc200062q. View

Guo L, Ren J, Jiang X . Perspectives on brain-targeting drug delivery systems. Curr Pharm Biotechnol. 2012; 13(12):2310-8. DOI: 10.2174/138920112803341770. View

SantaCruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M . Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005; 309(5733):476-81. PMC: 1574647. DOI: 10.1126/science.1113694. View

Abuirmeileh A, Lever R, Kingsbury A, Lees A, Locke I, Knight R . The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease. Eur J Neurosci. 2007; 26(2):417-23. DOI: 10.1111/j.1460-9568.2007.05653.x. View

Wohlfart S, Gelperina S, Kreuter J . Transport of drugs across the blood-brain barrier by nanoparticles. J Control Release. 2011; 161(2):264-73. DOI: 10.1016/j.jconrel.2011.08.017. View

10.

Wang Y, Cooke M, Lapitsky Y, Wylie R, Sachewsky N, Corbett D . Transport of epidermal growth factor in the stroke-injured brain. J Control Release. 2010; 149(3):225-35. DOI: 10.1016/j.jconrel.2010.10.022. View

11.

Sun Y, Jin K, Xie L, Childs J, Mao X, Logvinova A . VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003; 111(12):1843-51. PMC: 161428. DOI: 10.1172/JCI17977. View

12.

Denyer R, Douglas M . Gene therapy for Parkinson's disease. Parkinsons Dis. 2012; 2012:757305. PMC: 3353142. DOI: 10.1155/2012/757305. View

13.

Pardridge W . Blood-brain barrier drug targeting enables neuroprotection in brain ischemia following delayed intravenous administration of neurotrophins. Adv Exp Med Biol. 2003; 513:397-430. DOI: 10.1007/978-1-4615-0123-7_15. View

14.

Joshi S, Chavhan S, Sawant K . Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm. 2010; 76(2):189-99. DOI: 10.1016/j.ejpb.2010.07.007. View

15.

Sindhu K, Saravanan K, Mohanakumar K . Behavioral differences in a rotenone-induced hemiparkinsonian rat model developed following intranigral or median forebrain bundle infusion. Brain Res. 2005; 1051(1-2):25-34. DOI: 10.1016/j.brainres.2005.05.051. View

16.

Wang Z, Cheng S, Ma M, Ma Y, Yang J, Xu G . Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia. Neurosci Lett. 2008; 446(1):30-5. DOI: 10.1016/j.neulet.2008.09.030. View

17.

ROBERTS W, Delaat J, Nagane M, Huang S, Cavenee W, Palade G . Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Am J Pathol. 1998; 153(4):1239-48. PMC: 1853053. DOI: 10.1016/S0002-9440(10)65668-4. View

18.

Sarin H, Kanevsky A, Wu H, Brimacombe K, Fung S, Sousa A . Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells. J Transl Med. 2008; 6:80. PMC: 2639552. DOI: 10.1186/1479-5876-6-80. View

19.

Wu H, Li J, Zhang Q, Yan X, Guo L, Gao X . A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-β₂₅₋₃₅-treated rats following intranasal administration. Eur J Pharm Biopharm. 2011; 80(2):368-78. DOI: 10.1016/j.ejpb.2011.10.012. View

20.

Kim I, Lim C, Kim J, Nam H, Nam K, Kim S . Neuroprotection by biodegradable PAMAM ester (e-PAM-R)-mediated HMGB1 siRNA delivery in primary cortical cultures and in the postischemic brain. J Control Release. 2009; 142(3):422-30. DOI: 10.1016/j.jconrel.2009.11.011. View