Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, 6th of October City, Giza 12585, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Int J Biol Macromol. 2023 Mar 31;232:123458. doi: 10.1016/j.ijbiomac.2023.123458. Epub 2023 Jan 26.
Irritant contact dermatitis (ICD) is an inflammatory skin condition characterized by severe eczematous lesions. Nanoparticulate drug delivery is the most predominant way to improve dermal penetration and have gained remarkable recognition for targeted delivery of therapeutic payload and reduced off-target effects. Therefore, the current work aimed to fabricate polyelectrolyte complex nanoparticles (PENPs) containing two natural biodegradable polymers namely; chitosan (CS) and hyaluronic acid (HA) to deliver the non steroidal anti-inflammatory drug etoricoxib (ETX) to the deeper skin layers to alleviate any systemic toxicity and improve its therapeutic efficacy against ICD. ETX loaded-PENPs were prepared and optimized utilizing three independent variables; CS: HA mass ratio, chitosan solution pH and molecular weight of chitosan. Following the various physicochemical optimizations, the optimum ETX-loaded PENPs formulation (N1 0.15 %) exhibited spherical nature with an average diameter of 267.9 ± 9.4 nm, Polydispersity index of 0.366 ± 0.02, and positive zeta potential (+32.9 ± 0.47 mV). The drug was successfully entrapped and the entrapment efficiency reached 95 ± 0.2 %. N1 0.15 % formula showed efficient dermal targeting by significantly enhanced percentage of ETX permeated and retained in the various skin layers in comparison to ETX conventional gel during the ex-vivo skin permeation experiments. Furthermore, N1 0.15 % exhibited superior anti-inflammatory properties in vivo compared to ETX conventional gel in dithranol induced mice ear dermatitis. Conclusively, ETX-loaded PENPs could be a promising therapeutic approach for effecient management of ICD.
刺激性接触性皮炎 (ICD) 是一种炎症性皮肤病，其特征为严重的湿疹样病变。纳米颗粒药物递送是改善皮肤渗透的最主要方法，并且因其能够靶向递送达治疗有效载荷和减少脱靶效应而得到了显著认可。因此，目前的工作旨在制备包含两种天然可生物降解聚合物的聚电解质复合物纳米颗粒 (PENP)，即壳聚糖 (CS) 和透明质酸 (HA)，以将非甾体抗炎药依托考昔 (ETX) 递送至更深的皮肤层，以减轻任何全身毒性并提高其对 ICD 的治疗效果。利用三个独立变量（CS:HA 质量比、壳聚糖溶液 pH 值和壳聚糖分子量）制备和优化 ETX 负载 PENP。经过各种物理化学优化，最佳 ETX 负载 PENP 配方（N1 0.15%）表现出球形，平均直径为 267.9±9.4nm，多分散指数为 0.366±0.02，正zeta 电位为+32.9±0.47mV。药物成功包封，包封效率达到 95±0.2%。与 ETX 常规凝胶相比，N1 0.15%在体外皮肤渗透实验中显著增加了 ETX 在各个皮肤层中的渗透和保留百分比，表明其具有高效的皮肤靶向性。此外，与 ETX 常规凝胶相比，N1 0.15%在二羟萘诱导的小鼠耳皮炎模型中表现出更好的抗炎性能。总之，ETX 负载 PENP 可能是一种有前途的治疗方法，可有效治疗 ICD。
