Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Med-X Center for Materials, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.
J Control Release. 2024 Apr;368:318-328. doi: 10.1016/j.jconrel.2024.02.043. Epub 2024 Mar 4.
Dry eye disease (DED) is a common and frequent ocular surface disease worldwide, which can cause severe ocular surface discomfort and blurred vision. Inflammation and reactive oxygen species (ROS) play decisive roles in the development of DED. However, existing treatments usually focus on anti-inflammation while ignore the role of ROS in DED. Ever worse, the clinical preparations are easily cleared by nasolacrimal ducts, resulting in poor therapeutic effect. To circumvent these obstacles, here we designed a phenylboronic acid (PBA) modified liposome co-loading immunosuppressant cyclosporin A (CsA) and antioxidant crocin (Cro). The CsA/Cro PBA Lip achieved mucoadhesion through the formation of covalent bonds between PBA and the sialic acid residues on mucin, and consequently improved the retention of drugs on the ocular surface. By inhibiting ROS production and blocking NF-κB inflammatory pathway, CsA/Cro PBA Lip successfully promoted the healing of damaged corneal epithelium, eventually achieving the goal of relieving DED. CsA/Cro PBA Lip is proven a simple yet effective dual-drug delivery system, exhibiting superior antioxidant and anti-inflammatory effects both in vitro and in vivo. This approach holds great potential in the clinical treatment of DED and other related mucosal inflammations.
干眼症（DED）是一种常见且频繁发生的眼表疾病，可导致严重的眼表不适和视力模糊。炎症和活性氧（ROS）在 DED 的发展中起决定性作用。然而，现有的治疗方法通常侧重于抗炎，而忽略了 ROS 在 DED 中的作用。更糟糕的是，临床制剂很容易被鼻泪管清除，导致治疗效果不佳。为了克服这些障碍，我们在这里设计了一种苯硼酸（PBA）修饰的载免疫抑制剂环孢素 A（CsA）和抗氧化剂西红花苷（Cro）的脂质体。CsA/Cro PBA Lip 通过 PBA 与粘蛋白上的唾液酸残基之间形成共价键实现了粘膜黏附，从而提高了药物在眼表面的滞留。通过抑制 ROS 的产生和阻断 NF-κB 炎症途径，CsA/Cro PBA Lip 成功促进了受损角膜上皮的愈合，最终实现了缓解 DED 的目标。CsA/Cro PBA Lip 被证明是一种简单而有效的双重药物递送系统，在体外和体内均显示出优异的抗氧化和抗炎作用。这种方法在 DED 和其他相关黏膜炎症的临床治疗中具有很大的潜力。
