α-Lipoic acid (LA), a dithiol micronutrient, acts as a vital cofactor in various cellular catabolic reactions and is also known as a universal antioxidant. The therapeutic efficacy of LA is compromised by a poor aqueous solubility as well as a short halflife. In the present study, LA was conjugated to D-α-tocopherol polyethylene glycol succinate (TPGS) using carbodiimideacid− alcohol coupling reaction. The synthesized conjugate (TPGS-LA) was characterized using 1 H and 13 C nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), UV−vis spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The TPGS-LA conjugate was demonstrated to be biocompatible and to have better anticonvulsion activity as compared to native LA in pentylenetetrazol (PTZ)-induced convulsions in zebrafish. Moreover, zebrafish larvae pretreated with TPGS-LA conjugate demonstrated a significant (p < 0.05) reduction of protein carbonylation levels and downregulation of c-fos expression during seizures as compared to native LA. Conclusively, the present findings demonstrate that the TPGS-LA conjugate can be a promising approach for the delivery of LA.

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