Viscosupplementation consists of hyaluronic acid (HA) intra-articular injections, commonly applied for osteoarthritis treatment while non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered for pain relief. Here, HA and a NSAID (celecoxib) were combined in a formulation based on a low transition temperature mixture (LTTM) of glycerol:sorbitol, reported to increase celecoxib’s solubility, thus rendering a potential alternative viscosupplement envisioning enhanced therapeutic efficiency. The inclusion of glucosamine, a cartilage precursor, was also studied. The developed formulations were assessed in terms of rheological properties, crucial for viscosupplementation: the parameters of crossover frequency, storage (G’) and loss (G’’) moduli, zero-shear-rate viscosity, stable viscosity across temperatures, and shear thinning behaviour, support viscoelastic properties suitable for viscosupplementation. Additionally, the gels biocompatibility was confirmed in chondrogenic cells (ATDC5). Regarding drug release studies, high and low clearance scenarios demonstrated an increased celecoxib (CEX) release from the gel (6 to 73-fold), compared to dissolution in PBS. The low clearance setup presented the highest and most sustained CEX release, highlighting the importance of the gel structure in CEX delivery. NMR stability studies over time demonstrated the LTTM+HA+CEX (GHA+CEX) gel as viable candidate for further evaluation. In sum, the features of GHA+CEX support its potential use as alternative viscosupplement.

中文翻译：

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基于低转变温度混合物的粘稠补充剂辅以塞来昔布治疗骨关节炎

粘液补充剂包括关节内注射透明质酸 (HA)，通常用于治疗骨关节炎，而非甾体类抗炎药 (NSAID) 则广泛用于缓解疼痛。在此，HA 和 NSAID（塞来昔布）组合在基于甘油：山梨醇的低转变温度混合物 (LTTM) 的配方中，据报道可增加塞来昔布的溶解度，从而提供一种潜在的替代粘稠补充剂，有望提高治疗效率。还研究了软骨前体葡萄糖胺的含量。开发的配方根据流变特性进行评估，这对于粘性补充至关重要：交叉频率、储存模量 (G') 和损耗模量 (G'')、零剪切速率粘度、不同温度下的稳定粘度和剪切稀化参数行为，支持适合粘性补充的粘弹性。此外，凝胶的生物相容性在软骨细胞（ATDC5）中得到证实。关于药物释放研究，高清除率和低清除率情况表明，与 PBS 中的溶解相比，塞来考昔 (CEX) 从凝胶中的释放增加（6 至 73 倍）。低间隙设置呈现出最高且最持续的 CEX 释放，突出了凝胶结构在 CEX 递送中的重要性。随着时间的推移，NMR 稳定性研究表明 LTTM+HA+CEX (GHA+CEX) 凝胶是进一步评估的可行候选材料。总之，GHA+CEX 的特性支持其作为替代粘胶补充剂的潜在用途。