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Intrathecal Drug Delivery in the Era of Nanomedicine

Credits: None available.

Intrathecal Drug Delivery in the Era of Nanomedicine

Learning Objectives

As a result of participating in this activity, learners will be able/better able to:

  • Devise pharmaceutical treatment plans for my patients


Learn state-of-the-art strategies for intrathecal (IT) drug delivery via nanomedicine. 

Nanomedicine-delivered agents allow for new targets and greater efficacy of delivery for therapeutic molecules, imaging agents, and genes to reach the surfaces of the brain and spinal cord. In some cases, evidence suggests that these compounds may reach parenchymal structures. 

Several IT nanomedicine have reached clinical trail or been clinically approved for use in humans, and research is into accelerating. IT delivery of nanoparticles has found utility in preclinical models of CNS disease, including pain, neuroinflammation, infection, metabolism, neurotrauma, neurovascular disease, behavior and cancer. 

This presentation combines preclinical and clinical literature describing the use of various forms of nanomedicine in an IT context.


  • Intrathecal concepts: where drugs go, how they can be delivered
    • Anatomy and physiology of the subarachnoid space (SAS)
    • CSF flow and exchange
    • Drug movement
    • Limitations
  • Biomaterials and nanoparticles
    • The relation between carrier and payload properties
    • Colloid design for IT administration
  • Nanomedicine trials and emerging therapies in pain management 

Desirable Physician Attributes

  • Medical Knowledge [ACGME/ABMS] about established and evolving biomedical, clinical, and cognate (e.g. epidemiological and social-behavioral) sciences and the application of this knowledge to patient care.
  • Employ Evidence-based Practice [IOM] Integrate best research with clinical expertise and patient values for optimum care and participate in learning and research activities to the extent feasible.

Accreditation & Designation

Release date: This activity was released 8/27/2021.

Termination date: The content of this activity remains eligible for CME Credit until 8/26/2024, unless reviewed or amended prior to this date.

Neurovations Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Neurovations Education designates this other activity (blended learning) for a maximum of 0.75 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure of Financial Relationships & Measures to Resolve of Conflicts of Interest

[Presenter] Rachael Sirianni discloses the following financial relationships within the past 24 months: Consulting: Ian’s Friends Foundation, Exicure, Inc., Zulia Biotech

No other person with control of, or responsibility for, the planning, delivery, or evaluation of accredited continuing education has, or has had within the past 24 months, financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships have been mitigated. Materials were reviewed in advance of the activity by person(s) that do not have conflicts of interest related to the content. In some cases, content may have been modified as part of the review and mitigation process. All clinical recommendations are evidence-based and free of commercial bias (e.g., peer-reviewed literature, adhering to evidence-based practice guidelines).

Additional Reading

  • Fowler, M. J., Cotter, J. D., Knight, B. E., Sevick-Muraca, E. M., Sandberg, D. I., & Sirianni, R. W. (2020). Intrathecal drug delivery in the era of nanomedicine. Advanced Drug Delivery Reviews, 165, 77-95.
  • Householder, K. T., Dharmaraj, S., Sandberg, D. I., Wechsler-Reya, R. J., & Sirianni, R. W. (2019). Fate of nanoparticles in the central nervous system after intrathecal injection in healthy mice. Scientific Reports, 9(1), 1-11.
  • Medina, D. X., Chung, E. P., Teague, C. D., Bowser, R., & Sirianni, R. W. (2020). Intravenously administered, retinoid activating nanoparticles increase lifespan and reduce neurodegeneration in the SOD1G93A mouse model of ALS. Frontiers in Bioengineering and Biotechnology, 8, 224.
  • Chimento, Adele, Francesca De Amicis, Rosa Sirianni, Maria Stefania Sinicropi, Francesco Puoci, Ivan Casaburi, Carmela Saturnino, and Vincenzo Pezzi. "Progress to improve oral bioavailability and beneficial effects of resveratrol." International Journal of Molecular Sciences 20, no. 6 (2019): 1381.
  • Huber, J. D., Witt, K. A., Hom, S., Egleton, R. D., Mark, K. S., & Davis, T. P. (2001). Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression. American Journal of Physiology-Heart and Circulatory Physiology, 280(3), H1241-H1248.
  • DosSantos, M. F., Holanda-Afonso, R. C., Lima, R. L., DaSilva, A. F., & Moura-Neto, V. (2014). The role of the blood–brain barrier in the development and treatment of migraine and other pain disorders. Frontiers in Cellular Neuroscience, 8, 302.
  • Kempuraj, D., Mentor, S., Thangavel, R., Ahmed, M. E., Selvakumar, G. P., Raikwar, S. P., ... & Zaheer, A. (2019). Mast cells in stress, pain, blood-brain barrier, neuroinflammation and Alzheimer’s disease. Frontiers in Cellular Neuroscience, 13, 54.
  • Wolka, A. M., Huber, J. D., & Davis, T. P. (2003). Pain and the blood–brain barrier: obstacles to drug delivery. Advanced Drug Delivery Reviews, 55(8), 987-1006.
  • Brooks, T. A., Hawkins, B. T., Huber, J. D., Egleton, R. D., & Davis, T. P. (2005). Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations. American Journal of Physiology-Heart and Circulatory Physiology, 289(2), H738-H743.
  • D Skaper, S. (2016). Mast Cell–glia dialogue in chronic pain and neuropathic pain: blood-brain barrier implications. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 15(9), 1072-1078.


  • 0.75 - Physician
  • 0.75 - Non-Physician