Triamcinolone Acetonide (TCA)-Loaded Biodegradable Microspheres Improve Therapeutic Outcomes in Thyroid-Associated Ophthalmopathy (TAO) by Reducing Fibrosis and Adipogenesis.

Abstract

Thyroid-associated ophthalmopathy (TAO) is an inflammatory orbital disease linked to thyroid dysfunction, leading to fibrosis and adipogenesis, which compromise visual acuity and quality of life. Triamcinolone acetonide (TCA) is effective in managing inflammation; however, it is limited by delivery challenges and side effects. This study evaluates TCA-loaded biodegradable microspheres (TCA@MS) as a controlled-release system to improve TCA's therapeutic efficacy in TAO. It was hypothesized that TCA@MS would enhance drug uptake, reduce fibrosis, and inhibit adipogenesis in TAO models. The TCA@MS was prepared and characterized for drug loading and release, showing 95% release within 7 days. The average diameter of TCA@MS is approximately 365 nm. The TCA@MS demonstrated a drug loading efficiency of approximately 10% and an encapsulation efficiency of around 55%. In vitro, TCA@MS enhanced TCA uptake, reduced fibrosis marker levels, and inhibited adipogenic differentiation in transforming growth factor beta 1 (TGF-β1)-induced human orbital fibroblasts (OFs). In vivo, TCA@MS intraorbital injection treatment of TAO mice decreased adipose tissue, inflammatory cell infiltration, and collagen deposition more effectively than free TCA intraorbital injection treatment. The fibrosis (CTGF, collagen I), proliferative marker (ki-67), and adipogenesis markers (PPARγ) were also downregulated by TCA@MS treatment in TAO mice. These findings suggest that TCA@MS offers a promising delivery system for localized treatment of TAO, providing sustained therapeutic effects with reduced adverse outcomes.