Sze-Wing Mok1,2, Sai-Chuen Fu1,2, Yau-Chuk Cheuk1,2, I-Ming Chu3, Kai-Ming Chan1,2, Ling Qin1,2, Shu-Hang Yung1,2, Ki-Wai Kevin Ho1,2. 1. Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. 2. Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. 3. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Abstract
OBJECTIVE: Quercetin (Que), a bioflavonoid, is both anti-inflammatory and antioxidative. Que has been used as an oral supplement for osteoarthritis (OA) with inconsistent findings because of its low bioavailability. We encapsulated Que in a mPEG-polypeptide thermogel to prolong its bioactivity. The efficacy of this formulation was evaluated in a posttraumatic OA rat model. DESIGN: Methoxy-poly(ethylene glycol)-l-poly(alanine) (mPEG-PA) polymer was synthesized and characterized in terms of cytotoxicity and release kinetics in vitro. At 12 weeks old, Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT). At 24 weeks post-operation, rats received either an intra-articular (IA) injection of saline, hydrogel, or hydrogel with Que (50 or 500 μg). Gait analysis was performed at pre-ACLT, pre-treatment, and at 4, 8, and 12 weeks post-treatment. At 12 weeks post-treatment, knee joints were collected for histopathological evaluation. RESULTS: In vitro studies showed that chondrocytes were viable after 72 hours of incubation with mPEG-PA, and the release of Que could be sustained for >28 days. Among all OA rats, the limb idleness index (LII) were significantly increased at 24 weeks post-ACLT. Rats that received hydrogel with Que (50 μg) showed the most reduction in LII at both 4 and 8 weeks post-treatment. The Osteoarthritis Research Society International score of rats received hydrogel with Que (50 μg) was significantly lower than the control group. All rats suffered from low-grade synovitis (Krenn score: 2-4). CONCLUSION: This study suggests that a sustained delivery of Que (50 μg) could provide symptom relief and also delay the progression of OA in the knee.
OBJECTIVE:Quercetin (Que), a bioflavonoid, is both anti-inflammatory and antioxidative. Que has been used as an oral supplement for osteoarthritis (OA) with inconsistent findings because of its low bioavailability. We encapsulated Que in a mPEG-polypeptide thermogel to prolong its bioactivity. The efficacy of this formulation was evaluated in a posttraumatic OA rat model. DESIGN:Methoxy-poly(ethylene glycol)-l-poly(alanine) (mPEG-PA) polymer was synthesized and characterized in terms of cytotoxicity and release kinetics in vitro. At 12 weeks old, Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT). At 24 weeks post-operation, rats received either an intra-articular (IA) injection of saline, hydrogel, or hydrogel with Que (50 or 500 μg). Gait analysis was performed at pre-ACLT, pre-treatment, and at 4, 8, and 12 weeks post-treatment. At 12 weeks post-treatment, knee joints were collected for histopathological evaluation. RESULTS: In vitro studies showed that chondrocytes were viable after 72 hours of incubation with mPEG-PA, and the release of Que could be sustained for >28 days. Among all OA rats, the limb idleness index (LII) were significantly increased at 24 weeks post-ACLT. Rats that received hydrogel with Que (50 μg) showed the most reduction in LII at both 4 and 8 weeks post-treatment. The Osteoarthritis Research Society International score of rats received hydrogel with Que (50 μg) was significantly lower than the control group. All rats suffered from low-grade synovitis (Krenn score: 2-4). CONCLUSION: This study suggests that a sustained delivery of Que (50 μg) could provide symptom relief and also delay the progression of OA in the knee.
Entities:
Keywords:
chondroprotective; drug delivery system; osteoarthritis; quercetin
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