Tetrandrine-loaded phenylboronic acid-chitosan nanoparticles for enhanced corneal penetration and anti-fibrotic...

Postoperative corneal haze, driven by aberrant TGF-β1-mediated fibrosis, remains a formidable clinical challenge following refractive surgery. Current steroid therapies are compromised by severe side effects, including steroid-induced glaucoma. Herein, we report a nanoparticle (CCB@TET) comprising a tetrandrine-loaded bovine serum albumin core and a 3-carboxyphenylboronic acid-modified chitosan shell for corneal haze prevention. The optimized nanoplatform (202 nm, +35 mV) exhibited high drug loading (39.25%) and sustained release. The shell coating endowed dual transport mechanisms: mucoadhesion via electrostatic interaction and reversible tight junction opening via occludin downregulation, facilitating enhanced transcorneal permeation. In vitro, CCB@TET suppressed human corneal stromal cell migration and myofibroblast transdifferentiation without compromising epithelial wound healing. In a rabbit transepithelial photorefractive keratectomy haze model, topical CCB@TET outperformed free tetrandrine and clinical fluorometholone, while avoiding steroid-induced intraocular pressure elevation. Mechanistically, CCB@TET was found to suppress the TGF-β1/Smad signaling cascade through ITGB6 downregulation, as revealed by transcriptomic screening and biochemical validation. This study presents a rationally designed nanoplatform for safe and effective prevention of postoperative corneal haze.