Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Colloids Surf B Biointerfaces. 2023 Aug;228:113399. doi: 10.1016/j.colsurfb.2023.113399. Epub 2023 Jun 10.
Meloxicam (MLX) is prescribed for the management of pain and inflammation allied with osteoarthritis (OA). However, MLX causes intestinal damage in long term administration. Hence, meloxicam loaded emulgel (MLX-emulgel) was optimized, formulated and examined under stringent parameters in monosodium-iodoacetate (MIA) induced knee OA in Wistar rats.
Nanoemulsion of MLX was fabricated by ultrasonication and microfluidization method with a droplet size of 66.81 ± 5.31-nm and zeta potential of -24.6 ± 0.72-mV. Further, MLX nanoemulsion was optimized with centrifugation, heating-cooling cycles and transmittance parameters in addition to scale-up feasibility with microfluidizer. Post optimization, MLX-nanoemulsion was tailored as emulgel with Carbopol Ultrez 10 NF and assessed for pH, rheology, textural properties, assay and stability features. The in-vitro release study revealed the Korsmeyer-Peppas release kinetics and ex-vivo skin permeation was improved by 6.71-folds. The skin distribution of MLX-emulgel evinced the transfollicular mode of permeation. In-vivo study indicated the protective action of MLX-emulegl expressed in terms of inflammatory cyctokines level, X-ray analysis of knee joints of rats, histopathology and OARSI (Osteoarthritis Research Society International) scoring. MLX-emulgel treated group displayed lower (P < 0.001) level of COX-2 intensity as compared to positive control group. However, it was comparable (P > 0.05) to the normal control group, MLX oral dispersion, i.v. solution and etoricoxib gel groups. MLX-emulgel showcased an alternative to the long term usage of analgesics for relieving the symptoms of knee OA.
MLX-emulgel may be a potential candidate for translating in to a clinically viable dosage form in the management of knee OA.
美洛昔康（MLX）用于治疗骨关节炎（OA）相关的疼痛和炎症。然而，长期使用 MLX 会导致肠道损伤。因此，我们在单钠碘乙酸（MIA）诱导的 Wistar 大鼠膝骨关节炎模型下，对载美洛昔康乳凝胶（MLX-Emulgel）进行了优化、制备和严格的参数检测。
采用超声和微流法制备 MLX 纳米乳，粒径为 66.81±5.31nm，Zeta 电位为-24.6±0.72mV。此外，还通过离心、加热-冷却循环和透光率参数对 MLX 纳米乳进行了优化，并采用微流仪进行了放大可行性研究。优化后，将 MLX-纳米乳制成卡波姆 Ultrez 10 NF 乳凝胶，并对其 pH 值、流变学、质构特性、含量测定和稳定性进行了评估。体外释放研究表明，释放符合 Korsmeyer-Peppas 动力学，经皮渗透提高了 6.71 倍。MLX-Emulgel 的皮肤分布显示出经毛囊渗透的模式。体内研究表明，MLX-Emulgel 的保护作用表现在炎症细胞因子水平、大鼠膝关节 X 射线分析、组织病理学和 OARSI（骨关节炎研究协会国际）评分上。与阳性对照组相比，MLX-Emulgel 组 COX-2 强度（P<0.001）降低，但与正常对照组、MLX 口服分散剂、静脉溶液和依托考昔凝胶组相当。MLX-Emulgel 为长期使用镇痛药缓解膝骨关节炎症状提供了一种替代选择。
MLX-Emulgel 可能成为治疗膝骨关节炎的一种有潜力的临床可行剂型。
