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. 2025 May;20(9):943-954.
doi: 10.1080/17435889.2025.2487410. Epub 2025 Apr 5.

PLGA nanoparticle-mediated anti-inflammatory gene delivery for the treatment of neuropathic pain

Boomin Choi  1 , Subeen Lee  2 , Seohyun Chung  1 , Ellane Eda Barcelona  3 , Jinpyo Hong  1 , Sung Joong Lee  1   2
Affiliations

PLGA nanoparticle-mediated anti-inflammatory gene delivery for the treatment of neuropathic pain

Boomin Choi et al. Nanomedicine (Lond). 2025 May.

Abstract

Aim: This study aimed to mitigate neuropathic pain behavior in a sciatic nerve transection (SNT)-induced mouse model by delivering anti-inflammatory cytokines - interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta 1 (TGF-β1) - via poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).

Materials & methods: Upon gene delivery of IL-4, IL-10, and TGF- β1, the anti-inflammatory effects and induction of microglia M2 polarization were evaluated. Plasmid (IL-4, IL-10, and TGF-β1)-encapsulated PLGA NPs (PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1) were synthesized and characterized for size, zeta potential, cellular toxicity, and cellular uptake. The analgesic effect of anti-inflammatory gene delivery using PLGA NPs was then assessed in a mouse model of neuropathic pain.

Results: Gene delivery of IL-4, IL-10, and TGF-β1 showed a significant anti-inflammatory effect in LPS-treated cells and IL-4 strongly promoted microglia M2 polarization in vitro. PLGA NPs successfully delivered the anti-inflammatory cytokine-coding genes into mouse spinal cord cells, specifically targeting microglia. PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1 NPs produced analgesic effects in a SNT-induced mouse neuropathic pain model. Notably, PLGA@IL-4 demonstrated the most effective and remarkably long-lasting analgesic effect, strongly enhancing microglia M2 polarization in spinal cord microglia.

Conclusion: Gene therapy using PLGA NPs for overexpression of anti-inflammatory cytokines could be a promising strategy for the treatment of neuropathic pain.

Keywords: IL-10; IL-4; Microglia; TGF-β1; gene delivery; nanoparticle; neuropathic pain; poly(d,l-lactic-co-glycolic acid).

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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