Epigallocatechin-3-gallate loaded proliposomal vesicles for management of traumatic brain injury: In-vitro and in-vivo evaluation

• Published in: Journal of drug delivery science and technology 2024-08, Vol.97, p.105745, Article 105745
• Main Authors: Al-Najjar, Aya H., Khalifa, Maha K.A., Amin, Omnya M., Badawi, Noha M.
• Format: Article
• Language: English
• Subjects: Epigallocatechin-3-gallate; Oxidative stress biomarkers; Proliposomes; Sirt1/Nrf2/HO-1 signaling pathway; Slurry technique; Traumatic brain injury
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2024.105745

One of the primary causes of disability and mortality worldwide is traumatic brain injury (TBI). Oxidative stress is one of the main pathological cascades of TBI. Therefore, finding an effective antioxidant for TBI is a challenge. Several studies revealed that Epigallocatechin-3-gallate (EGCG) had neuroprotective properties, so it might play an important role in TBI. However, it has some drawbacks including instability that may lead to reduced efficacy which could be enhanced using nanoformulation. Consequently, this study aimed to design and optimize EGCG-loaded Proliposomes (EGCG-PLs) and to investigate the antioxidant effect against TBI in rats by modulating the Sirt1/Nrf2/HO-1 signaling pathway. EGCG-PLs were formulated by the slurry technique. Then, to choose the best formula, nanovesicles were assessed and optimized by the Box-Behnken Design to determine the effect of preparation factors on the formed vesicles. Following that, we used an animal model of TBI to compare the neuroprotective effects of the optimized formula to the free drug in vivo. To confirm the neuroprotective action, oxidative stress biomarkers were evaluated as well as histopathological examinations of different brain tissues were performed. The optimized EGCG-loaded PLs formula had a mean size of 150.63 ± 2.65 nm while the percentage of entrapment efficiency was 89.744 ± 0.89 %. The EGCG in vitro release from the optimized PLs formula was prolonged in comparison with the free EGCG. The optimized formula showed a superior antioxidant effect compared to its free counterpart as it significantly decreased MDA and increased the endogenous antioxidants, SOD, and GSH, of brain tissues in addition to activation of the Sirt1/Nrf2/HO-1 signaling pathway. Furthermore, amelioration of histopathological alterations induced by TBI in brain tissues was more prominent with EGCG-PLs treatment. To conclude, all outcomes point to a potential enhancement in the efficacy of EGCG when prepared in PLs in combating TBI. [Display omitted]