# PLGA Nanoparticles as a Localized Therapy for Experimental Autoimmune Neuritis?

> **NIH VA IK2** · EDWARD HINES JR VA HOSPITAL · 2020 · —

## Abstract

Inflammatory peripheral neuropathies constitute one of the largest and least understood spectrums of
neurologic disorders. Among these disorders is acute inflammatory demyelinating polyneuropathy (AIDP), a
disabling inflammatory autoimmune disease of the peripheral nervous system. Inflammatory peripheral
neuropathies collectively represent a major socioeconomic strain to our Veteran patient population and to the
Veterans Health Administration. Despite overwhelming prevalence and socioeconomic impact, the treatment
options available for Veterans suffering from inflammatory peripheral neuropathies, including AIDP, remain
palliative, nonspecific, and ineffective.
 Immunization of susceptible strains of laboratory animals with peripheral nerve myelin P2 peptide and
adjuvant induces experimental autoimmune neuritis (EAN), which closely models the pathogenicity of AIDP.
Statins, a group of established cholesterol lowering agents, therapeutically attenuate EAN by inhibiting the
transendothelial migration of autoreactive leukocytes into peripheral nerves. The effect of statins on the
immune system is now known to be pleiotropic. Our lab has demonstrated that statins specifically attenuate
TNF-α mediated release of the chemokine CCL2 from the peripheral nerve microvascular endoneurial
endothelial cells (PNMECs) that form the blood-nerve barrier (BNB).
 Poor bioavailability necessitates high systemic doses to achieve the pleiotropic effects of statins, and rare
but serious side effects preclude clinical translation. Biomaterials-based drug delivery represents a novel
means by which to administer drugs that exhibit low bioavailability and high systemic toxicity. Poly(lactic-co-
glycolic)acid (PLGA) can be used to form biodegradable nanoparticles that encapsulate hydrophobic
compounds, including statins, for controlled release. In addition, PLGA can be modified to express moieties
that direct circulating particles to sites of inflammation, allowing for targeted systemic administration.
 In this CDA-2 application, our objective is to determine the therapeutic potential of a novel, targeted
drug delivery system to modulate endothelial GTPase signaling at the inflamed peripheral nerve. To
accomplish this, we will utilize PLGA nanoparticles that encapsulate lovastatin and are surface-functionalized
with purified macrophage plasma membranes. We hypothesize that targeted disruption of endothelial
GTPase signaling with functionalized, lovastatin-encapsulating nanoparticles will therapeutically
limit CCL2-dependent trafficking of autoreactive leukocytes in EAN. This will be tested using in vitro and
in vivo approaches. First, we will assess the ability of surface-functionalized, PLGA nanoparticles to adhere
to, migrate across, and deliver a payload within the activated BNB in vitro. Second, we will determine the
therapeutic potential of targeting the inflamed BNB with systemically-administered, surface-functionalized,
lovastatin-encapsulating nanoparticles in EAN. T...

## Key facts

- **NIH application ID:** 9934880
- **Project number:** 5IK2RX002305-04
- **Recipient organization:** EDWARD HINES JR VA HOSPITAL
- **Principal Investigator:** Kelly A Langert
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934880

## Citation

> US National Institutes of Health, RePORTER application 9934880, PLGA Nanoparticles as a Localized Therapy for Experimental Autoimmune Neuritis? (5IK2RX002305-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934880. Licensed CC0.

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