pH-Sensitive Degradable Poly(ortho ester)-Polyesters As Injectable Viscous Fluid for Long-Acting Rheumatoid Arthritis Treatment

This study focuses on the development and evaluation of injectable drug delivery systems for the long-acting treatment of rheumatoid arthritis. Four types of poly(ortho ester)-polyesters (POC2, POC3, POL2, and POL3) were synthesized by the polycondensation reactions between an ortho ester diamine monomer and the active esters of oligocaprolactone diols (A-OCL) or oligolactide diols (A-OLA) with different molecular weights and exhibited discrepant zero-shearing viscosities and hydrophilic–hydrophobic properties. The degradation behaviors were collectively controlled by surface erosion and bulk degradation mechanisms, and the accelerated degradation at pH 5.0 was observed due to acid-responsive hydrolysis of ortho ester and ester groups. Consequently, the release of indomethacin (IND) was well sustained with the kinetics fitting of the Ritger–Peppas model. After being injected subcutaneously once into adjuvant-induced arthritis rats, the formulation IND-POC2 slowly released IND for up to 14 days and showed the best therapeutic effects on effectively alleviating the swelling of joints, bone erosion, and the expression of pro-inflammatory factors. To sum up, this research demonstrated the cheerful prospect of the obtained functional viscous poly(ortho ester)-polyester fluid for sustained drug release in rheumatoid arthritis disease.