Guiding Diffusion of Magnetic Nanoparticles from Nose to the Brain Using Permanent Magnet is Theoretically Feasible but Practically Challenging

Authors

  • Partam Manalai Mary Washington Hospital
  • Stephen Lin Howard University, USA
  • Shabeer A. Manalai Intuitive Insight, Inc, USA
  • Charles Scercy Mary Washington Hospital, USA
  • Patricia Harrison Mary Washington Hospital, USA
  • Najeeb Manalai Intuitive Insight, Inc, USA
  • Mansoor Malik Johns Hopkins University, USA

Abstract

The blood-brain barrier (BBB) presents a significant challenge in delivering medications to the brain, impeding direct targeting of specific brain regions in humans. Currently, effective methods for overcoming this protective barrier are limited. Targeted drug delivery to the brain from the nose has been utilized successfully, albeit the delivered dose of medication directly to the brain predominantly depends on circulation. One promising strategy involves guiding magnetic nanoparticles through the cribriform plate from the nose to the brain. Unlike other areas, the nose and circumventricular organs provide a less restrictive pathway where the BBB is permeable. The concept of guiding the diffusion of magnetic nanoparticles through the cribriform plate appears feasible in theory. However, the complexity of such a delivery system necessitates a heuristic approach for practical implementation. In our recent study, we attempted to guide the diffusion of fluorescent magnetic nanoparticles using neodymium magnets in different media and animal brain tissues. Although, we did not successfully demonstrate this method of delivery with simplistic approach, we argue that an interprofessional effort is essential to tackle this mode of drug delivery by passing the challenges posed by the BBB and to innovate targeted drug delivery solutions for the brain. By leveraging diverse perspectives and specialized knowledge, we can advance towards more effective therapies that harness the potential of magnetic nanoparticle technology for neurological treatments.

Keywords: magnetic nanoparticles, targeted drug delivery, nasal drug delivery, bypass blood brain barrier, olfactory epithelium

Keywords:

magnetic nanoparticles, targeted drug delivery, nasal drug delivery, bypass blood brain barrier, olfactory epithelium

DOI

https://doi.org/10.22270/jddt.v14i9.6797

Author Biographies

Partam Manalai, Mary Washington Hospital

Howard University, USA

Intuitive Insight, Inc, USA

Stephen Lin, Howard University, USA

Howard University, USA

Shabeer A. Manalai, Intuitive Insight, Inc, USA

Intuitive Insight, Inc, USA

Charles Scercy, Mary Washington Hospital, USA

Mary Washington Hospital, USA

Patricia Harrison, Mary Washington Hospital, USA

Mary Washington Hospital, USA

Najeeb Manalai, Intuitive Insight, Inc, USA

Virginia Health Sciences at Old Dominion University, USA

Mansoor Malik, Johns Hopkins University, USA

Johns Hopkins University, USA

References

Nutt, D. J. & Attridge, J. CNS drug development in Europe - Past progress and future challenges. Neurobiology of Disease 2014;61 https://doi.org/10.1016/j.nbd.2013.05.002 PMid:23685094

DiBonaventura, M., Gabriel, S., Dupclay, L., Gupta, S. & Kim, E. A patient perspective of the impact of medication side effects on adherence: Results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry 2012;12. https://doi.org/10.1186/1471-244X-12-20 PMid:22433036 PMCid:PMC3342101

Stroup, T. S. et al. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: Schizophrenia trial design and protocol development. Schizophrenia Bulletin vol. 2003;29. https://doi.org/10.1093/oxfordjournals.schbul.a006986 PMid:12908658

Baldessarini, R., Henk, H., Sklar, A., Chang, J. & Leahy, L. Psychotropic medications for patients with bipolar disorder in the United States: Polytherapy and adherence. Psychiatric Services 2008;59. https://doi.org/10.1176/appi.ps.59.10.1175 PMid:18832504

Pachter, J. S., De Vries, H. E. & Fabry, Z. The blood-brain barrier and its role in immune privilege in the central nervous system. Journal of Neuropathology and Experimental Neurology 2003 ;62. https://doi.org/10.1093/jnen/62.6.593 PMid:12834104

Wong, A. D. et al. The blood-brain barrier: An engineering perspective. Frontiers in Neuroengineering 2013. https://doi.org/10.3389/fneng.2013.00007 PMid:24009582 PMCid:PMC3757302

Benarroch, E. E. Circumventricular organs: Receptive and homeostatic functions and clinical implications. Neurology 2011;77. https://doi.org/10.1212/WNL.0b013e31822f04a0 PMid:21931109

Kamei, N. & Takeda-Morishita, M. Strategy for peptide drug delivery via nose-to-brain transport pathways: Challenges to pharmacotherapy for dementia. Drug Delivery System (2019; 34. https://doi.org/10.2745/dds.34.360

Sipos, E. et al. Intranasal delivery of human β-amyloid peptide in rats: Effective brain targeting. Cell Mol Neurobiol 2010;30. https://doi.org/10.1007/s10571-009-9463-6 PMid:19806448

C.D., C. et al. Intranasal treatment of central nervous system dysfunction in humans. Pharmaceutical Research vol. 2013;30.

Chapman, C. D. et al. Intranasal treatment of central nervous system dysfunction in humans. Pharmaceutical Research 2013; 30. https://doi.org/10.1007/s11095-012-0915-1 PMid:23135822 PMCid:PMC3761088

Nakashima, T., Kimmelman, C. P. & Snow, J. B. Structure of Human Fetal and Adult Olfactory Neuroepithelium. Arch Otolaryngol 1984; 110. https://doi.org/10.1001/archotol.1984.00800360013003 PMid:6477257

Lane, A. P. Nasal anatomy and physiology. Facial Plastic Surgery Clinics of North America2004;12. https://doi.org/10.1016/j.fsc.2004.04.001 PMid:15337106

LaMantia, A. S., Bhasin, N., Rhodes, K. & Heemskerk, J. Mesenchymal/epithelial induction mediates olfactory pathway formation. Neuron. 2000;28. https://doi.org/10.1016/S0896-6273(00)00121-5 PMid:11144352

Key, B. Molecular development of the olfactory nerve pathway. in Annals of the New York Academy of Sciences vol. 1998; 855. https://doi.org/10.1111/j.1749-6632.1998.tb10548.x PMid:9929588

Morrison, E. E. & Costanzo, R. M. Morphology of olfactory epithelium in humans and other vertebrates. Microsc Res Tech 1992;23. https://doi.org/10.1002/jemt.1070230105 PMid:1392071

Rombaux, P., Duprez, T. & Hummel, T. Olfactory bulb volume in the clinical assessment of olfactory dysfunction. Rhinology vol. 2009;47.

Paik, S. I., Seiden, A. M., Duncan, H. J., Smith, D. V. & Lehman, M. N. Human Olfactory Biopsy: The Influence of Age and Receptor Distribution. Arch Otolaryngol Head Neck Surg 1992;118. https://doi.org/10.1001/archotol.1992.01880070061012 PMid:1627295

Cowan, C. M. & Roskams, A. J. Apoptosis in the mature and developing olfactory neuroepithelium. Microsc Res Tech 58, (2002). https://doi.org/10.1002/jemt.10150 PMid:12203699

Wu, H., Hu, K. & Jiang, X. From nose to brain: Understanding transport capacity and transport rate of drugs. Expert Opinion on Drug Delivery 2008;5. https://doi.org/10.1517/17425247.5.10.1159 PMid:18817519

Shapiro, B. et al. Shaping magnetic fields to direct therapy to ears and eyes. Annual Review of Biomedical Engineering 2014;16. https://doi.org/10.1146/annurev-bioeng-071813-105206 PMid:25014789

Loomba, L. & Scarabelli, T. Metallic nanoparticles and their medicinal potential. Part II: Aluminosilicates, nanobiomagnets, quantum dots and cochleates. Therapeutic Delivery 2013;4. https://doi.org/10.4155/tde.13.74 PMid:24024515

Cheng, R., Meng, F., Deng, C., Klok, H. A. & Zhong, Z. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials 2013;34. https://doi.org/10.1016/j.biomaterials.2013.01.084 PMid:23415642

chemicell-GmbH. Material Safety Data Sheet: nano-screenMAG-ARA. http://www.chemicell.com/products/Magnetic_microparticle/Magnetic_microparticles.html .

Bernad, S. I. & Bernad, E. Magnetic Forces by Permanent Magnets to Manipulate Magnetoresponsive Particles in Drug-Targeting Applications. Micromachines (Basel) 2022;13. https://doi.org/10.3390/mi13111818 PMid:36363839 PMCid:PMC9698488

Shapiro, B. et al. Open challenges in magnetic drug targeting. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015;7. https://doi.org/10.1002/wnan.1311 PMid:25377422 PMCid:PMC4397114

Daquinag, A. C., Souza, G. R. & Kolonin, M. G. Adipose tissue engineering in three-dimensional levitation tissue culture system based on magnetic nanoparticles. Tissue Eng Part C Methods 2013;19. https://doi.org/10.1089/ten.tec.2012.0198 PMid:23017116 PMCid:PMC3603558

Kim, W. J. & Trumper, D. L. High-precision magnetic levitation stage for photolithography. Precis Eng 1998;22. https://doi.org/10.1016/S0141-6359(98)00009-9

Hahn, I. Heuristic structural optimization of the permanent magnets used in a surface mounted permanent-magnet synchronous machine. IEEE Trans Magn 2012;48. https://doi.org/10.1109/TMAG.2011.2167980

Crumlish, N. & Kelly, B. D. How psychiatrists think. Advances in Psychiatric Treatment 2009;15. https://doi.org/10.1192/apt.bp.107.005298

Marewski, J. N. & Gigerenzer, G. Heuristic decision making in medicine. Dialogues in Clinical Neuroscience 2012;14. https://doi.org/10.31887/DCNS.2012.14.1/jmarewski PMid:22577307 PMCid:PMC3341653

Deacon, B. J. The biomedical model of mental disorder: A critical analysis of its validity, utility, and effects on psychotherapy research. Clinical Psychology Review 2013;33. https://doi.org/10.1016/j.cpr.2012.09.007 PMid:23664634

LaFollette, H. & Shanks, N. Brute Science: Dilemmas of Animal Experimentation. Philosophical issues in science 1996.

Serani-Merlo, A., Paz, R. & Castillo, A. The 'whole-animal approach' as a heuristic principle in neuroscience research. Biological Research 2005; 38 https://doi.org/10.4067/S0716-97602005000400008

LaFollette, H. & Shanks, N. Animal models in biomedical research: some epistemological worries. Public Aff Q 1993;7.

Sato, R. C. esar & Sato, G. T. iemy K. Probabilistic graphic models applied to identification of diseases. Einstein (Sao Paulo) 2015;13. https://doi.org/10.1590/S1679-45082015RB3121 PMid:26154555 PMCid:PMC4943832

Published

2024-09-15
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How to Cite

1.
Manalai P, Lin S, Manalai SA, Scercy C, Harrison P, Manalai N, et al. Guiding Diffusion of Magnetic Nanoparticles from Nose to the Brain Using Permanent Magnet is Theoretically Feasible but Practically Challenging. J. Drug Delivery Ther. [Internet]. 2024 Sep. 15 [cited 2026 Jan. 13];14(9):100-6. Available from: https://jddtonline.info/index.php/jddt/article/view/6797

How to Cite

1.
Manalai P, Lin S, Manalai SA, Scercy C, Harrison P, Manalai N, et al. Guiding Diffusion of Magnetic Nanoparticles from Nose to the Brain Using Permanent Magnet is Theoretically Feasible but Practically Challenging. J. Drug Delivery Ther. [Internet]. 2024 Sep. 15 [cited 2026 Jan. 13];14(9):100-6. Available from: https://jddtonline.info/index.php/jddt/article/view/6797