开发基于壳聚糖/羧甲基纤维素钠的地塞米松聚电解质复合物,用于治疗前葡萄膜炎。

Md Ali Mujtaba, Harita Desai, Anju Ambekar, Ritesh Fule, Shriya Pande, Musarrat Husain Warsi, Gamal Osman Elhassan, Murtada Taha, Khalid Anwer, Tarkeshwar Devidas Golghate
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引用次数: 0

摘要

前葡萄膜炎是最常见的眼部炎症之一,由感染、外伤和其他特发性疾病引起,如果治疗不当,可导致完全失明。 因此,本研究旨在配制和评估负载地塞米松磷酸钠(DSP)的聚电解质复合物(PEC)纳米粒子(NPs),用于治疗前葡萄膜炎。将低分子量壳聚糖和阴离子聚合物羧甲基纤维素混合,通过复合物共凝结形成了负载 DSP 的 PEC-NPs 。采用 Box-Behnken 设计对配方进行了优化,并评估了自变量的影响:壳聚糖浓度、CMC 浓度和壳聚糖溶液的 pH 值对因变量:颗粒(PS)、多分散指数(PDI)、配方的 pH 值和截留率(%EE)的影响。优化配方的 PS、PDI、ZP 和 pH 值分别为 451±82.0995nm、0.3807±0.1862、+20.33±1.04mV 和 6.8367±0.0737。制剂的EE%和载药量分别为61.66±4.2914%和21.442±1.814%。优化制剂的体外药物释放研究显示,药物释放时间延长至 12 小时,而市售制剂在 1 小时和 6 小时内的猝灭释放率分别为 85.625±4.3062% 和 98.1462±3.0921%。傅立叶变换红外光谱研究表明,药物有效地融入了 PEC-NPs 制剂中,而 DSC 和 XRD 研究则表明药物在制剂中呈非晶态。TEM 研究显示了自组装的近似球形的核壳纳米结构。角膜渗透研究表明,与市售制剂相比,PEC-NPs 的药物渗透率更高。对优化配方进行的 HET-CAM 测试表明,该配方对眼部用药无刺激且安全。因此,负载 DSP 的 PEC-NPs 能够通过延长角膜前滞留时间和持续释放药物来提高生物利用度,是传统滴眼液的有效替代品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development of chitosan/sodium carboxymethyl cellulose-based polyelectrolyte complex of dexamethasone for treatment of anterior uveitis.

Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose (CMC). The formulations were optimized using Box-Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle size (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, zeta potential, and pH of the optimized formulation were found 451 ± 82.0995 nm, 0.3807 ± 0.1862, +20.33 ± 1.04 mV and 6.8367 ± 0.0737 respectively. The %EE and drug loading of formulation were 61.66 ± 4.2914% and 21.442 ± 1.814% respectively.In vitrodrug release studies of optimized formulation showed the prolonged release up to 12 h whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 h and 98.1462 ± 3.0921% at 6 h, respectively. Fourier transform infrared studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas differential scanning calorimetry and x-ray diffraction studies showed the amorphized nature of the drug in the formulation. Transmission electron microscopy study showed self-assembled, nearly spherical, core-shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. Hen's Eggs test-Chorioallantoic Membrane test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release.

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