Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, Post Office, P.O. Box 21521, Alexandria, Egypt.
Sci Rep. 2024 Sep 18;14(1):21744. doi: 10.1038/s41598-024-71456-6.
Despite its long history as a preferential cyclooxygenase-2 inhibitor, the topical application of etodolac in inflammatory disorders does not achieve the desired clinical efficiency because of its poor water solubility and poor skin permeation. In the ongoing study, phosalosomes were designed to mitigate the etodolac drawbacks and to enhance its skin localization. Hyaluronic acid was utilized to prepare a dermal gel for the alleviation of skin inflammation. Etodolac loaded hyaluronic acid phosalosomal gel had a sustainable release profile and 10.59-fold enhanced skin retention compared to free etodolac, with boosted skin tolerability on histopathological examination after acute and chronic applications. Confocal laser microscopy imaging indicated that the etodolac amounts accumulated in the liver and kidney following dermal application were 29 and 5.7-fold lower than those following the systemic dose, respectively. For in vivo studies, etodolac loaded hyaluronic acid phosalosomal gel presented superior anti-oedemic and significant anti-nociception potential. The promising homogenous localization highlighted its potential for the delivery of lipophilic drugs for the targeted treatment of other localized skin disorders.
尽管依托度酸作为一种优先的环氧化酶-2 抑制剂具有悠久的历史，但由于其较差的水溶性和较差的皮肤渗透性，其在炎症性疾病中的局部应用并不能达到预期的临床效果。在正在进行的研究中，设计了 phosalosomes 来减轻依托度酸的缺点，并增强其皮肤定位。利用透明质酸制备用于缓解皮肤炎症的真皮凝胶。与游离依托度酸相比，负载依托度酸的透明质酸 phosalosomal 凝胶具有可持续释放的特点，皮肤滞留性增强了 10.59 倍，在急性和慢性应用后的组织病理学检查中，皮肤耐受性得到了提高。共聚焦激光显微镜成像表明，与全身剂量相比，经皮应用后，依托度酸在肝脏和肾脏中的积累量分别降低了 29 倍和 5.7 倍。在体内研究中，负载依托度酸的透明质酸 phosalosomal 凝胶表现出优异的抗水肿和显著的镇痛潜力。有希望的均匀定位突出了其用于递送至其他局部皮肤疾病的靶向治疗的亲脂性药物的潜力。
