Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Arar, Saudi Arabia.
Department of Pharmaceutics, Bombay College of Pharmacy, Santacruz East, Mumbai 400098, India.
Biomed Mater. 2024 Oct 3;19(6). doi: 10.1088/1748-605X/ad7e6b.
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.drug 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.
前葡萄膜炎是由感染、创伤和其他特发性疾病引起的最常见的眼部炎症形式之一,如果治疗不当,它可导致完全失明。因此,本研究旨在研制和评价磷酸地塞米松(DSP)负载聚电解质复合物(PEC)纳米粒(NPs)治疗前葡萄膜炎。DSP 负载 PEC-NPs 通过混合低分子量壳聚糖和阴离子聚合物羧甲基纤维素(CMC)通过复凝聚形成。通过 Box-Behnken 设计优化配方,并评价独立变量对依赖变量的影响:壳聚糖浓度、CMC 浓度和壳聚糖溶液的 pH 值对以下依赖变量的影响:粒径(PS)、多分散指数(PDI)、配方的 pH 值和包封效率(%EE)。优化配方的 PS、PDI、Zeta 电位和 pH 值分别为 451 ± 82.0995nm、0.3807 ± 0.1862、+20.33 ± 1.04mV 和 6.8367 ± 0.0737。配方的%EE 和药物载量分别为 61.66 ± 4.2914%和 21.442 ± 1.814%。优化配方的药物释放研究表明,药物可延长释放至 12 小时,而市售配方在 1 小时内释放 85.625 ± 4.3062%,在 6 小时内释放 98.1462 ± 3.0921%。傅里叶变换红外研究表明,药物有效地掺入 PEC-NPs 配方中,而差示扫描量热法和 X 射线衍射研究表明,药物在配方中具有无定形性质。透射电子显微镜研究表明,自组装形成近球形核壳纳米结构。角膜渗透研究表明,与市售制剂相比,药物从 PEC-NPs 中的渗透更高。优化配方的鸡胚试验-绒毛尿囊膜试验表明,该制剂对眼部给药无刺激性且安全。因此,由于其通过更长的预角膜滞留时间和持续的药物释放来提高生物利用度的能力,DSP 负载 PEC-NPs 是常规滴眼剂的有效替代品。