Targeted Drug Delivery in Neurodegenerative Diseases: the Role of Nanotechnology

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2025 Feb 18

PMID 39963432

Authors

Rupal Dhariwal

Mukul Jain

Yaser Rafiq Mir

Abhayveer Singh

Bhavik Jain

Pankaj Kumar

Mohd Tariq

Devvret Verma

Khemraj Deshmukh

Virendra Kumar Yadav

Tabarak Malik

Affiliations

Soon will be listed here.

Abstract

Neurodegenerative diseases, characterized by progressive neuronal loss and cognitive impairments, pose a significant global health challenge. This study explores the potential of nanotherapeutics as a promising approach to enhance drug delivery across physiological barriers, particularly the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (B-CSFB). By employing nanoparticles, this research aims to address critical challenges in the diagnosis and treatment of conditions such as Alzheimer's, Parkinson's, and Huntington's diseases. The multifactorial nature of these disorders necessitates innovative solutions that leverage nanomedicine to improve drug solubility, circulation time, and targeted delivery while minimizing off-target effects. The findings underscore the importance of advancing nanomedicine applications to develop effective therapeutic strategies that can alleviate the burden of neurodegenerative diseases on individuals and healthcare systems.

References

Takeda T, Kitagawa K, Arai K . Phenotypic variability and its pathological basis in amyotrophic lateral sclerosis. Neuropathology. 2019; 40(1):40-56. DOI: 10.1111/neup.12606. View

ORoak B, Vives L, Girirajan S, Karakoc E, Krumm N, Coe B . Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. 2012; 485(7397):246-50. PMC: 3350576. DOI: 10.1038/nature10989. View

Zhao M, Li X, Xu C, Zou L . Efficacy and safety of nerve growth factor for the treatment of neurological diseases: a meta-analysis of 64 randomized controlled trials involving 6,297 patients. Neural Regen Res. 2015; 10(5):819-28. PMC: 4468778. DOI: 10.4103/1673-5374.156989. View

Wang L, Wang X, Deng L, Zhang H, He B, Cao W . Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders. Int Immunopharmacol. 2022; 113(Pt B):109436. PMC: 9661988. DOI: 10.1016/j.intimp.2022.109436. View

Pirhaghi M, Mamashli F, Moosavi-Movahedi F, Arghavani P, Amiri A, Davaeil B . Cell-Penetrating Peptides: Promising Therapeutics and Drug-Delivery Systems for Neurodegenerative Diseases. Mol Pharm. 2024; 21(5):2097-2117. DOI: 10.1021/acs.molpharmaceut.3c01167. View

Krupa P, Svobodova B, Dubisova J, Kubinova S, Jendelova P, Machova Urdzikova L . Nano-formulated curcumin (Lipodisq™) modulates the local inflammatory response, reduces glial scar and preserves the white matter after spinal cord injury in rats. Neuropharmacology. 2019; 155:54-64. DOI: 10.1016/j.neuropharm.2019.05.018. View

Hebert L, Weuve J, Scherr P, Evans D . Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013; 80(19):1778-83. PMC: 3719424. DOI: 10.1212/WNL.0b013e31828726f5. View

Gamez-Valero A, Guisado-Corcoll A, Herrero-Lorenzo M, Solaguren-Beascoa M, Marti E . Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases. Antioxidants (Basel). 2020; 9(11). PMC: 7695195. DOI: 10.3390/antiox9111095. View

Tabrizi S, Flower M, Ross C, Wild E . Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol. 2020; 16(10):529-546. DOI: 10.1038/s41582-020-0389-4. View

10.

Modi G, Pillay V, Choonara Y . Advances in the treatment of neurodegenerative disorders employing nanotechnology. Ann N Y Acad Sci. 2010; 1184:154-72. DOI: 10.1111/j.1749-6632.2009.05108.x. View

11.

Wang S, Lu W, Tovmachenko O, Rai U, Yu H, Ray P . Challenge in Understanding Size and Shape Dependent Toxicity of Gold Nanomaterials in Human Skin Keratinocytes. Chem Phys Lett. 2013; 463(1-3):145-149. PMC: 3780398. DOI: 10.1016/j.cplett.2008.08.039. View

12.

Cai Q, Jeong Y . Mitophagy in Alzheimer's Disease and Other Age-Related Neurodegenerative Diseases. Cells. 2020; 9(1). PMC: 7017092. DOI: 10.3390/cells9010150. View

13.

Kurkinen M . Lecanemab (Leqembi) is not the right drug for patients with Alzheimer's disease. Adv Clin Exp Med. 2023; 32(9):943-947. DOI: 10.17219/acem/171379. View

14.

Metselaar J, Wauben M, Wagenaar-Hilbers J, Boerman O, Storm G . Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes. Arthritis Rheum. 2003; 48(7):2059-66. DOI: 10.1002/art.11140. View

15.

Arranja A, Pathak V, Lammers T, Shi Y . Tumor-targeted nanomedicines for cancer theranostics. Pharmacol Res. 2016; 115:87-95. PMC: 5412956. DOI: 10.1016/j.phrs.2016.11.014. View

16.

Weiss M, Fan J, Claudel M, Sonntag T, Didier P, Ronzani C . Density of surface charge is a more predictive factor of the toxicity of cationic carbon nanoparticles than zeta potential. J Nanobiotechnology. 2021; 19(1):5. PMC: 7789233. DOI: 10.1186/s12951-020-00747-7. View

17.

Abbott N, Patabendige A, Dolman D, Yusof S, Begley D . Structure and function of the blood-brain barrier. Neurobiol Dis. 2009; 37(1):13-25. DOI: 10.1016/j.nbd.2009.07.030. View

18.

Liu W, Dong X, Liu Y, Sun Y . Photoresponsive materials for intensified modulation of Alzheimer's amyloid-β protein aggregation: A review. Acta Biomater. 2021; 123:93-109. DOI: 10.1016/j.actbio.2021.01.018. View

19.

Singh S, Shi T, Duffin R, Albrecht C, van Berlo D, Hohr D . Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: role of the specific surface area and of surface methylation of the particles. Toxicol Appl Pharmacol. 2007; 222(2):141-51. DOI: 10.1016/j.taap.2007.05.001. View

20.

Debnath K, Pradhan N, Singh B, Jana N, Jana N . Poly(trehalose) Nanoparticles Prevent Amyloid Aggregation and Suppress Polyglutamine Aggregation in a Huntington's Disease Model Mouse. ACS Appl Mater Interfaces. 2017; 9(28):24126-24139. DOI: 10.1021/acsami.7b06510. View