Co-delivery of anti-inflammatory and antioxidant agents via polymersomes for osteoarthritis therapy

TL;DR

This study develops a polymersome-based system to deliver anti-inflammatory and antioxidant agents for treating osteoarthritis, showing improved therapeutic effects in a rat model.

Contribution

A novel polymersome co-delivery system for cordycepin and phenylboronic acid is developed, demonstrating enhanced therapeutic efficacy for osteoarthritis.

Findings

The co-loaded polymersomes showed potent ROS-scavenging ability and reduced inflammatory cytokines in vitro.

In a rat model, the polymersomes significantly reduced cartilage damage and promoted regeneration compared to other treatments.

The system provided sustained release and improved joint targeting, resulting in superior therapeutic outcomes.

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease primarily driven by inflammation and oxidative stress. This study aimed to develop a polymersome-based co-delivery system encapsulating hydrophilic cordycepin and hydrophobic phenylboronic acid (PBA) to enhance their solubility, stability, and therapeutic efficacy against OA.

Formulation parameters were optimized using a Taguchi orthogonal design to achieve high encapsulation efficiency, sustained drug release, and effective reactive oxygen species (ROS) scavenging. In vitro anti-inflammatory effects were evaluated in LPS-activated RAW 264.7 macrophages by assessing TNF-α, IL-1β, and extracellular ROS levels. Therapeutic efficacy was further validated in a papain-induced OA rat model treated with co-loaded polymersomes via intraperitoneal injection for four weeks, with joint swelling and serum cytokines monitored.

The optimized co-loaded polymersomes exhibited an average size of 101.03 ± 0.42 nm and a polydispersity index (PDI) of 0.248 ± 0.014. They demonstrated a H2O2-responsive compound release and potent ROS-scavenging ability. In vitro, the co-loaded polymersomes significantly reduced inflammatory cytokines and ROS levels. In OA rat model, co-loaded polymersomes led to the greatest reduction in cartilage damage and promoted cartilage regeneration compared to other treatment groups.

This co-delivery system offered a sustained release profile, enhanced joint targeting, and reduced adverse effects, resulting in superior therapeutic outcomes compared to free compounds alone or their combination. These findings highlighted its potential as a promising therapeutic approach for OA management.

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