Polydopamine-Coated Triamcinolone Acetonide Acetate Nanocrystals: Prevention of Postoperative Peritoneal Adhesion by Combining Anti-inflammation, Oxidative Stress Scavenging and Cytokine Adsorption

Abstract

Prevention of postoperative abdominal adhesion (PA) remains inadequately addressed by current clinical practice due to difficulties in precise regulation of inflammation and elimination of peroxidation products. This study proposed a polydopamine-coated triamcinolone acetonide acetate nanocrystal (TAA@PDA) to prevent peritoneal adhesions via the collective effects of TAA and PDA through multiple mechanisms, including anti-inflammatory effect, oxidative stress (ROS/RNS) scavenging, certain hemostatic ability and adsorption of pro-inflammatory cytokine by numerous amino/phenolic hydroxyl groups. TAA@PDA particles with a rod-like morphology and an average diameter of approximately 560 nm were successfully prepared via ball milling. TAA@PDA demonstrated excellent physical stability for up to 30 days, ensuring complete drug release within 7 days without sedimentation or aggregation. Anti-inflammatory and anti-oxidative capabilities of TAA@PDA were proven by their strong adsorption with pro-inflammatory cytokines (e.g., IL-6 and TNF-α), low adsorption capacity of anti-inflammatory IL-10 and ~80% efficiency in scavenging reactive oxygen/nitrogen species (ROS/RNS). TAA@PDA's adsorption of type I collagen and strong tissue adhesion rate demonstrated its retention capacity on the abdominal wall or organ surfaces. At the cellular level, TAA@PDA inhibited intracellular production of ROS, and effectively suppressed secretion of the inflammatory marker nitric oxide (NO). TAA@PDA exhibited certain hemostatic ability for small wound bleeding in abdominal injury. TAA@PDA significantly inhibited abdominal adhesion formation in PA model animals with a low incidence of severe adhesion (9.1%) which was only 1/8 that of the commercial anti-PA hyaluronic acid gel and 1/5 that of uncoated TAA NC, further supported by excellent anti-inflammatory performance and significantly reduced collagen deposition shown by pathological examination. In conclusion, this TAA@PDA might provide an efficient solution to prevent postoperative peritoneal adhesion by precise coordination between inflammatory microenvironment regulation and tissue protection.