Intra-articular delivery of flurbiprofen sustained release thermogel: improved therapeutic outcome of collagenase II-induced rat knee osteoarthritis

Abstract

Knee osteoarthritis (OA) is a common degenerative disease. Intra-articular administration of flurbiprofen is frequently employed in clinic to treat OA, while repeated injections are required because of the limited effective duration. To improve therapeutic outcome and prolong the treatment interval, a poly(e-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(e-caprolactone-co-lactide) (PCLA-PEG-PCLA) triblock copolymer based flurbiprofen thermosensitive gel for the sustained intra-articular drug delivery was designed in this study. The anti-OA effects of this flurbiprofen thermogel were investigated on collagenase II-induced rat knee OA model by multiple approaches and compared with that of conventional sodium hyaluronate and flurbiprofen injecta. In vitro drug release studies indicated that flurbiprofen was sustained released from the thermosensitive gel for more than three weeks. This sustained drug release system exerted comparable short-term analgesic effects and distinctly improved long-term analgesic efficacy in terms of the increased percentage of the total ipsilateral paw print intensity and the reduced Knee-Bend scores of OA rats. The inflammatory response was attenuated in the samples of flurbiprofen gel treated group by showing decreased IL-1, IL-6, and IL-11 levels in the joint fluid and down-regulated IL-1, IL-6, IL-11, COX-2, TNF-a, and NF-jB/p65 expression in the articular cartilages. The results suggest the suitability of thermosensitive copolymer PCLA-PEG-PCLA for sustained intra-articular effects of flurbiprofen and provide in vivo experimental evidence for potential clinical application of this flurbiprofen delivery system to better management of OA cases.

Design of Targeted Flurbiprofen Biomimetic Nanoparticles for Management of Arthritis: In Vitro and In Vivo Appraisal

“…From these results, we found that FLUR-loaded HA-BSA NPs exhibited the highest anti-nociceptive effect as compared to other formulations reflecting the role of HA in targeting CD44 receptors in joints and the characteristic anti-inflammatory effect of FLUR in inflamed joints. These results agree with those reported by Li et al [55] where FLUR-loaded gel and HA decreased knee bend scores in osteoarthritic rats.…”

“…Concerning FLUR, it has been reported by Li et al [55] that expression of TNF-α a IL-6 was decreased in joint tissue after intra-articular injection of HA, FLUR, FLUR fr thermosensitive gel, and FLUR thermosensitive gel but a more distinct reduction was o served in FLUR thermosensitive gel treated group.…”

“…In addition, another study reported by Li et al [55] where the ELISA assay revealed that intra-articular injection of FLUR thermosensitive gel showed a significant reduction in IL-6 levels in joint fluid compared to injection of HA alone reflecting the role of FLUR thermosensitive gel in reducing inflammation.…”

Engineering of hybrid anticancer drug-loaded polymeric nanoparticles delivery system for the treatment and care of lung cancer therapy

“…These NMs were discrete in 25 mL of released mediums formulated in different pH 5 and 7.4 by PBS with 0.2% Tween-80 solution, while the regulated releasing fresh medium was extracted from the deviancy shaker at 1500 RPM in 37 °C and an equal volume of complete new mediums was used. The UV spectrometer was used to examine the controlled drug release effects of 5FU and PRN, as previously mentioned (Wilems et al, 2015 ; Stein et al, 2018 ; Kang et al, 2019 ; Li et al, 2020a , 2020b ).…”

“…Owing to its ecofriendly accountability and bio-competitiveness, bio-degradable polymeric nanoparticles with appropriate dimensions, even surface diameter, and increased aqueous solubility have gotten a lot of attention (Liu et al, 2016 ; Zhang & Tung, 2017 ; Liu et al, 2019 ; Li et al, 2020a , 2020b ). In anticancer therapy, biomaterial fields, and medical diagnosis, a number of environmentally friendly NMs have been widely used.…”