Spanlastic nanovesicles for enhanced ocular delivery of vanillic acid: design, in vitro characterization, and in vivo anti-inflammatory evaluation

Abstract

Spanlastics are novel surfactant-based, elastic vesicular nanocarriers composed of spans and edge activators. The present work aims to exploit their special penetration enhancing properties to enhance the ophthalmic delivery of the versatile nutraceutical vanillic acid (VA), for treatment of ocular inflammation. VA-loaded spanlastics were formulated by ethanol injection method using Tween 80, sodium deoxy cholate or Tween 60 as edge activators (EA) at various Span 60: EA mass ratios. Vesicles were characterized for their particle size (PS), polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), surface morphology, in vitro release profile, thermal properties and long-term stability, in addition to in vivo anti-inflammatory efficacy of the selected formula in an endotoxin-induced uveitis model. Selected formulation composed of Span 60: Tween 80 at a mass ratio of 70:30 displayed smallest PS of 299.8 ± 9.97 nm, PDI of 0.386 ± 0.047, an acceptable EE%, as well as good physical stability for 3 months. According to clinical scoring, inflammatory mediators levels and histopathological examination, VA-loaded spanlastic formulation resulted in significant alleviation of inflammation compared to drug suspension (p < 0.05). Formulation of VA into spanlastic nanoformulation is a promising approach to improve its ocular permeability, absorption and anti-inflammatory activity providing a safer alternative to current regimens.