AUTHOR=Mokhtar Hatem I. , Khodeer Dina M. , Alzahrani Sharifa , Qushawy Mona , Alshaman Reem , Elsherbiny Nehal M. , Ahmed Esam Sayed , Abu El Wafa Esam Ghanem , El-Kherbetawy Mohamed K. , Gardouh Ahmed R. , Zaitone Sawsan A. TITLE=Formulation and characterization of cholesterol-based nanoparticles of gabapentin protecting from retinal injury JOURNAL=Frontiers in Chemistry VOLUME=12 YEAR=2024 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1449380 DOI=10.3389/fchem.2024.1449380 ISSN=2296-2646 ABSTRACT=Introduction

This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats.

Methods

We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6 weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10–20 mg/kg), and diabetic + GAB-SLNs (10–20 mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41 nm), high negative Zeta potential (−32.18 ± 0.98 mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape.

Results

GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF).

Conclusion

The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders.