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Discovery of a long-acting nanocrystal formulation of INND-2201, a new co-drug of pregabalin and palmitoylethanolamide with synergistic analgesic effects

Xiao-Min Han, Yang Xiao, Chao-Nan Huang, Ming-Yue Yin, Ben Xu, Yang-Yang Song, Tao Zhuang, Gui-Sen Zhang. Pharm Sci Adv. 2025 Nov 4:3:100099.

Laboratory studyOther animalsWith INND-2201 (a co-drug combining pregabalin and PEA, tested as a single conjugate molecule)

This study tested palmitoylethanolamide together with INND-2201 (a co-drug combining pregabalin and PEA, tested as a single conjugate molecule). Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
Mice (inflammatory and neuropathic pain models); microsomal stability test in vitro
Dose used in the study
Oral INND-2201 (ED50 4.43 mg/kg inflammatory pain, 5.54 mg/kg neuropathic pain); intramuscular INND-2201 nanocrystals, particle size 107.1±2.7 nm
Duration
Pain relief from intramuscular nanocrystals lasted up to 5 days
What was measured
Metabolic stability of INND-2201 into pregabalin and PEA; antinociceptive effects in inflammatory and neuropathic pain models; nanocrystal particle size; acute toxicity, muscular irritation, rotarod and open field safety tests.

What the authors reported

INND-2201 was slowly metabolised into pregabalin and PEA and produced synergistic antinociceptive effects orally, with ED50 values of 4.43 mg/kg (inflammatory pain) and 5.54 mg/kg (neuropathic pain). Intramuscular nanocrystals gave pain relief lasting up to 5 days in a chronic inflammatory pain model in mice, with a good safety profile on toxicity and motor tests.

Limits of this study

A mouse study of a novel synthetic co-drug, not PEA alone; it cannot show effect in people. The authors declare no competing interests.

Source

PubMed 41550657 · doi:10.1016/j.pscia.2025.100099

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.