Journal Article Epublish 1 citation
PubMed: 39861692 DOI: 10.3390/pharmaceutics17010044
Therapeutic Efficacy of Intranasal -Acetyl-L-Cysteine with Cell-Penetrating Peptide-Modified Polymer Micelles on Neuropathic Pain in Partial Sciatic Nerve Ligation Mice.
Pharmaceutics 17(1)
Authors: Hiroshi Nango, Ai Takahashi, Naoto Suzuki, Takumi Kurano, Saia Sakamoto, Taiki Nagatomo, Toyofumi Suzuki, Takanori Kanazawa, Yasuhiro Kosuge, Hiroko Miyagishi
Affiliations
- Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Japan.
- Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Japan.
- Department of Clinical Pharmacology, Graduate School of Biomedical Sciences, Tokushima University, 1-78-1 Shoumachi, Tokushima 770-8505, Japan.
Abstract
: We previously demonstrated that the intranasal administration of cell-penetrating Tat peptide-modified carrier, PEG-PCL-Tat, improves drug delivery to the central nervous system. This study aimed to evaluate the potential of the post-onset intranasal administration of -acetyl-L-cysteine (NAC) combined with PEG-PCL-Tat (NAC/PPT) for neuropathic pain. : Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice. Mechanical allodynia was assessed using the von Frey test on days 11-14 post-ligation. NAC or NAC/PPT was intranasally administered after pain onset. Western blotting and immunohistochemistry were conducted to evaluate ionized calcium-binding adapter molecule 1 (Iba-1) expression and microglial activation in the spinal cord. : Mechanical allodynia was exacerbated 11 days after the ligation in PSNL mice. The intranasal administration of NAC alone prevented allodynia exacerbation but failed to provide a therapeutic effect against allodynia in PSNL mice. In contrast, NAC/PPT administration ameliorated PSNL-induced tactile allodynia, with maximum efficacy seen 13 and 14 days after ligation. Western blotting demonstrated that Iba-1 levels tended to increase in PSNL mice compared to controls. This trend of increased Iba-1 levels in PSNL mice was attenuated by the administration of NAC/PPT, but not by NAC alone. Immunohistochemistry revealed an increased number of Iba-1-stained microglia in the ipsilateral spinal cord of PSNL mice, which were significantly suppressed by the administration of NAC/PPT. : These results suggest that the post-onset intranasal administration of NAC/PPT ameliorates mechanical allodynia by suppressing microglia induction and that intranasal delivery with PEG-PCL-Tat might be a useful tool for the pharmacological management of neuropathic pain.
MeSH
Microglia, Cell-Penetrating Peptides, Cells, Cysteine, Spinal Cord, Polymers, Pain, Micelles, Administration, Intranasal, Ligation, Sciatic Nerve, Therapeutics, Neuralgia, Spine