Abstract Present study deals with fabrication of macromolecular prodrugs (MPDs) of flurbiprofen (FLB) with hydroxyethylcellulose (HEC). FLB was activated using p-toluenesulfonyl chloride and reacted with pre-dissolved HEC to yield HEC-FLB conjugates 1–3. Resultant prodrugs showed moderate to high degree of substitution (DS: 0.40–1.74) and assembled into nanoparticles of 220–550 nm at water/DMSO interface. Pharmacokinetic studies of HEC-FLB conjugate revealed a tmax of 4.0 h indicating delayed release of FLB while t1/2 of 10.63 h indicated sustained release characteristics of the conjugate in rabbit model. Pharmacological studies revealed that HEC-FLB conjugates had immunomodulatory potential as results showed 34 and 36% inhibition of Interleukin-6 and tumor necrosis factor-α, respectively. A 79% inhibition of paw edema indicated anti-inflammatory properties of the conjugates. Cell viability studies indicated safety of the conjugates to L929 cell lines up to 24 h in the range of 2–10 mM. Moreover, thermal analysis indicated greater stability of MPDs than FLB.

中文翻译：

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基于羟乙基纤维素的氟比洛芬偶联物：合成、表征、药物和药理学应用

摘要 本研究涉及用羟乙基纤维素 (HEC) 制备氟比洛芬 (FLB) 的大分子前药 (MPD)。FLB 使用对甲苯磺酰氯活化，并与预溶解的 HEC 反应以产生 HEC-FLB 缀合物 1-3。所得前药显示出中等至高度的取代度（DS：0.40-1.74），并在水/DMSO 界面组装成 220-550 nm 的纳米颗粒。HEC-FLB 偶联物的药代动力学研究表明 tmax 为 4.0 小时，表明 FLB 延迟释放，而 10.63 小时的 t1/2 表明偶联物在兔模型中具有持续释放特性。药理学研究表明，HEC-FLB 偶联物具有免疫调节潜力，结果显示对白细胞介素 6 和肿瘤坏死因子 α 的抑制率分别为 34% 和 36%。79% 的爪水肿抑制表明缀合物具有抗炎特性。细胞活力研究表明，在 2-10 mM 范围内，偶联物对 L929 细胞系的安全性长达 24 小时。此外，热分析表明 MPD 的稳定性高于 FLB。