Biocompatible sinapic acid-loaded chitosan nanoparticles as a topical nanotherapy for uveitis in rats: Formulation, characterization, and anti-inflammatory efficacy.

Sinapic acid (SA), a naturally occurring polyphenol, exhibits diverse biological properties, including anti-inflammatory activity. Its potential in treating ocular inflammations remains underexplored. Ocular protective barriers and hydrophobicity of SA hinder its effective ocular delivery. To overcome these limitations, SA-loaded chitosan nanoparticles (SA-CSNPs) were developed. Characterization revealed nano-sized (234.7 nm), positively charged (+ 32.4 mV) SA-CSNPs with a narrow polydispersity index (0.304). XRD and FTIR analyses confirmed the amorphous state of encapsulated SA without adverse interactions. The swelling index of SA-CSNPs in simulated tear fluid (STF) was 2011 %, while the saturation solubility of SA-pure reached 502 μg/mL in STF containing SLS. SA-CSNPs exhibited 85.6 % drug release over 12 h, following first-order kinetics. Ocular suitability of SA-CSNPs was confirmed by pH (7.1), viscosity (12.2 mPa-sec) and mucoadhesiveness. SA-CSNPs demonstrated excellent stability (95.3 % drug content) over 3 months. In vitro cytotoxicity on rat corneal epithelial cells revealed excellent biocompatibility (>80 % viability). Topical SA-CSNPs abridged the production of MPO, IL-6 and TNF-α and suppressed NF-κB (p65) subunit translocation in LPS-induced uveitis rats. In vivo pharmacodynamics, including the histological examination of uveal tissues, revealed significant inhibition of LPS-induced ocular inflammation in rats by SA-CSNPs. These findings suggest the potential of SA-CSNPs for localized, controlled delivery of SA to prevent ocular inflammations. Long-term ocular tolerance and preclinical assessments would establish SA-CSNPs a promising therapy for ocular inflammations.