Microparticles-in-Thermoresponsive/Bioadhesive Hydrogels as a Novel Integrated Platform for Effective Intra-articular Delivery of Triamcinolone Acetonide

• DOI: 10.1021/acs.molpharmaceut.0c00126
• Publication Date: 2020-04-09T19:39:00Z
• Authors: May Abou-ElNour; Mahmoud E. Soliman; Athanasios Skouras; Luca Casettari; Ahmed S. Geneidi; Rania A. H. Ishak
• Keywords: Male; Drug Carriers; Polymers; Viscosity; Temperature; Hydrogels; 02 engineering and technology; Triamcinolone Acetonide; 01 natural sciences; Polyethylene Glycols; Rats; 0104 chemical sciences; Arthritis, Rheumatoid; Spectroscopy, Fourier Transform Infrared; Microscopy, Electron, Scanning; Animals; 0210 nano-technology

Intra-articular (IA) injection of thermoresponsive hydrogels coupled with microparticles (MPs) possess the benefit sustaining anti-inflammatory drug effect within joint cavity for rheumatoid arthritis treatment. Star-shaped poly(polyethylene glycol) methacrylate [Poly(PEGMA)] copolymers were synthesized using free radical polymerization technique and fully characterized. Triamcinolone acetonide (TA)-loaded PLA/mPEG–PDL MPs, previously optimized, integrated into copolymer solutions at various concentrations tested their gelation temperatures. The MPs-in-hydrogel formulations characterized scanning electron microscope (SEM), viscosity measurements, ex vivo bioadhesion, in vitro release studies. systems was assessed adjuvant-induced monoarthritic rat knee joints compared to Kenacort TA-loaded MPs. Two successfully synthesized; G-1 = poly(PEGMA188-ME-co-PEGMA475-ME) G-2 poly(PEGMA246-EE-co-PEGMA475-ME). Using tube inversion technique, gel formation found dependent on concentration. An irreversible aggregation obtained ≤10% (w/v), while a formed 20 30% (w/v) both upon increasing temperature. MP-hydrogel optimized temperatures 33 37 °C, respectively. SEM images revealed porous microstructures adsorption MP surfaces. formulas showed pseudoplastic behaviors, bioadhesion study confirmed bioadhesiveness excised cartilage. sustainment from MPs-hydrogels In studies proved superiority MP-in-hydrogels treatment induced arthritis, relative MPs alone, suggesting applicability this platform IA delivery.