Indomethacin microencapsulation by coaxial ultrasonic atomization intended for intraarticular administration

Abstract

Indomethacin (IND) is a non-steroidal anti-inflammatory drug (NSAID) with high efficacy in the treatment of rheumatic disorders. Nonetheless, its severe adverse effects limit its first-line and long-term use, and its rapid clearance from the joint prevents its local administration. This study aims to overcome those limitations by developing an intra-articular formulation of IND-loaded microparticles made of polymeric blends of Polyactive® 1000PEOT70PBT30 and Resomer® RG502. Formulations were prepared by coaxial ultrasonic atomization according to an experimental design to assess the influence of the polymeric composition and flow rates supplied to the nozzle over particle size, encapsulation efficiency and in vitro delivery profile. Nine formulations of spherical microparticles were developed and exhaustively characterized, showing high drug entrapment (56.2–81.32 %) and suitable mean particle size for intra-articular administration (22.8–82.6 μm). In vitro evaluation of IND-loaded microparticles in THP-1 macrophages demonstrated their biocompatibility and extensive internalization by THP-1 cells, supporting their potential for macrophage targeting and particle retention into the joint. Further, IND-loaded microparticles showed high anti-inflammatory activity in vitro, significantly reducing the production of IL-6 and TNF-α by LPS-stimulated macrophages. Overall, the results support the idea that IND-loaded microcapsules are a suitable drug delivery system for the intra-articular administration of indomethacin.