Intra-articular (IA) injection of thermo-responsive hydrogels coupled with microparticles (MPs) possess the benefit of sustaining the anti-inflammatory drug effect within the joint cavity for rheumatoid arthritis treatment. Star-shaped thermo-responsive 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, were integrated into the synthesized copolymer solutions at various concentrations, and tested for their gelation temperatures. The MPs-in-hydrogel formulations were characterized using scanning electron microscope (SEM), viscosity measurements, ex-vivo bio-adhesion and in-vitro release studies. The anti-inflammatory effect of integrated systems was assessed in adjuvant-induced mono-arthritic rat knee joints, and compared to Kenacort® and TA-loaded MPs. Two copolymers were successfully synthesized; G-1 = poly(PEGMA188-ME-co-PEGMA475-ME) and G-2 = poly(PEGMA246-EE-co-PEGMA475-ME). Using tube inversion technique, the gel formation was found dependent on copolymer concentration. An irreversible aggregation was obtained at copolymer concentrations ≤ 10% (w/v), while a gel was formed at 20 and 30% (w/v) of both copolymers upon increasing temperature. The MP-hydrogel formulations were optimized at 20 and 30% (w/v) of G-1 and G-2 with gelation temperatures of 33 and 37 °C, respectively. SEM images revealed the porous microstructures of hydrogels and their adsorption on MP surfaces. The integrated formulae showed pseudoplastic behaviours, while bio-adhesion study confirmed their bio-adhesiveness on excised cartilage. In-vitro release study confirmed drug sustainment from MPs-hydrogels compared to MPs. In-vivo studies proved the superiority of MP-in-hydrogels in treatment of induced arthritis, relative to Kenacort® and MPs alone, suggesting the applicability of this integrated platform in IA drug delivery.
Microparticles-in-Thermoresponsive/Bioadhesive Hydrogels as a Novel Integrated Platform for Effective Intra-articular Delivery of Triamcinolone Acetonide
Casettari, Luca;
2020
Abstract
Intra-articular (IA) injection of thermo-responsive hydrogels coupled with microparticles (MPs) possess the benefit of sustaining the anti-inflammatory drug effect within the joint cavity for rheumatoid arthritis treatment. Star-shaped thermo-responsive 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, were integrated into the synthesized copolymer solutions at various concentrations, and tested for their gelation temperatures. The MPs-in-hydrogel formulations were characterized using scanning electron microscope (SEM), viscosity measurements, ex-vivo bio-adhesion and in-vitro release studies. The anti-inflammatory effect of integrated systems was assessed in adjuvant-induced mono-arthritic rat knee joints, and compared to Kenacort® and TA-loaded MPs. Two copolymers were successfully synthesized; G-1 = poly(PEGMA188-ME-co-PEGMA475-ME) and G-2 = poly(PEGMA246-EE-co-PEGMA475-ME). Using tube inversion technique, the gel formation was found dependent on copolymer concentration. An irreversible aggregation was obtained at copolymer concentrations ≤ 10% (w/v), while a gel was formed at 20 and 30% (w/v) of both copolymers upon increasing temperature. The MP-hydrogel formulations were optimized at 20 and 30% (w/v) of G-1 and G-2 with gelation temperatures of 33 and 37 °C, respectively. SEM images revealed the porous microstructures of hydrogels and their adsorption on MP surfaces. The integrated formulae showed pseudoplastic behaviours, while bio-adhesion study confirmed their bio-adhesiveness on excised cartilage. In-vitro release study confirmed drug sustainment from MPs-hydrogels compared to MPs. In-vivo studies proved the superiority of MP-in-hydrogels in treatment of induced arthritis, relative to Kenacort® and MPs alone, suggesting the applicability of this integrated platform in IA drug delivery.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
