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. 2024;19(25):2099-2112.
doi: 10.1080/17435889.2024.2390349. Epub 2024 Sep 4.

Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting

Song I Kim  1   2 , Jiah Yang  3 , Juhee Shin  4 , Nara Shin  1   2 , Hyo Jung Shin  2 , Jiyong Lee  5 , Chan Noh  5 , Dong Woon Kim  6 , Sun Yeul Lee  5
Affiliations

Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting

Song I Kim et al. Nanomedicine (Lond). 2024.

Abstract

Aim: Amitriptyline (AMI) has been used to treat neuropathic pain. However, the clinical outcomes remain unsatisfactory, presumably due to a limited understanding of the underlying molecular mechanisms. Here, we investigated a drug repositioning strategy using a low-dose of AMI encapsulated in poly (D, L lactic-co-glycolic acid) (PLGA) nanoparticles (AMI NPs) for neuropathic pain, since PLGA nanoparticles are known to enhance delivery to microglia.Methods: We evaluated the anti-allodynic effects of AMI and AMI NPs on neuropathic pain by assessing behaviors and inflammatory responses in a rat model of spinal nerve ligation (SNL). While the anti-allodynic effect of AMI (30 μg) drug injection on SNL-induced neuropathic pain persisted for 12 h, AMI NPs significantly alleviated mechanical allodynia for 3 days.Results: Histological and cytokine analyses showed AMI NPs facilitated the reduction of microglial activation and pro-inflammatory mediators in the spinal dorsal horn. This study suggests that AMI NPs can provide a sustained anti-allodynic effect by enhancing the targeting of microglia and regulating the release of pro-inflammatory cytokines from activated microglia.Conclusion: Our findings suggest that the use of microglial-targeted NPs continuously releasing AMI (2 μg) as a drug repositioning strategy offers long-term anti-allodynic effects.

Keywords: PLGA nanoparticles; amitriptyline; microglia; neuropathic pain.

Plain language summary

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity 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.

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