Development of a Curcumin-Loaded Nanomicelles-Injectable Sustained-Release Hydrogel System for Modulating Oxidative...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Musculoskeletal Research

Background:

• Tendinopathy is a prevalent musculoskeletal condition often leading to tendon rupture if untreated.
• Current treatments for tendinopathy have limitations, including frequent administration requirements and lack of fully effective drugs.
• Curcumin (Cur) possesses anti-inflammatory and antioxidant properties but suffers from poor solubility and stability, hindering its clinical use.

Purpose of the Study:

• To develop a stable, injectable hydrogel system for sustained release of curcumin (Cur) to enhance tendinopathy treatment.
• To encapsulate curcumin into pluronic F127 nanomicelles (Cur-F127) to improve its solubility and stability.
• To incorporate Cur-F127 micelles into an oxidized hyaluronic acid (oxi-HA) and adipic acid dihydrazide (ADH) hydrogel for sustained drug delivery.

Main Methods:

• Curcumin was encapsulated into pluronic F127 nanomicelles (Cur-F127).
• Cur-F127 micelles were incorporated into an oxidized hyaluronic acid and adipic acid dihydrazide hydrogel (Cur-F127&gel).
• The physicochemical properties, biocompatibility, degradation, and drug release kinetics of the hydrogel were evaluated. In vivo efficacy was assessed in a rat tendinopathy model.

Main Results:

• Cur-F127 micelles exhibited a particle size of 20.14 nm, with high encapsulation efficiency (89.95%) and drug loading (5.57%).
• The Cur-F127&gel hydrogel demonstrated a porous 3D structure, good biocompatibility, and sustained curcumin release over 20 days without an initial burst.
• In vivo studies showed significant tendon repair, reduced inflammation, improved collagen alignment, restored mitochondrial protein expression, and alleviated oxidative stress in the rat tendinopathy model.

Conclusions:

• The injectable sustained-release hydrogel system effectively delivers curcumin for long-term tendinopathy repair.
• This formulation overcomes curcumin's poor solubility and stability, offering a promising therapeutic strategy for tendinopathy.
• The developed system holds significant potential for clinical application in treating tendinopathy and other musculoskeletal disorders requiring local, sustained drug delivery.