Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome
Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome
复制标题
苯硼酸系硫酸软骨素基粘膜粘附纳米结构脂质载体用于治疗干眼综合征
DOI：
10.1016/j.actbio.2019.08.035
复制
发表时间：
2019
影响因子：
9.7
通讯作者：
Pan Weisan
中科院分区：
文献类型：
--
作者：
Tan Guoxin;Li Jinyu;Song Yiming;Yu Yibin;Liu D;an;Pan Weisan
干眼症是一种常见的眼部疾病，影响世界各地的许多人。它通常用滴眼剂治疗，滴眼剂由于从眼表面快速清除而具有低生物利用度，并导致患者依从性差和副作用。为了提高治疗效果，制备了纳米结构脂质载体（NLC）负载的地塞米松（DEX），并用（3-氨甲基苯基）硼酸缀合硫酸软骨素（APBA-ChS）进行功能化。由于APBA具有硼酸基团，它可以与眼粘蛋白中存在的唾液酸形成高亲和力复合物，这有助于延长角膜滞留时间和改善药物递送。与滴眼液相比，罗丹明B（RhB）标记的APBA-ChS-NLC可显著延长在角膜表面的停留时间。此外，如刺激性研究和组织学图像所示，DEX-APBA-ChS-NLC对兔眼无刺激性。药效学研究表明，DEX-APBA-ChS-NLC能明显减轻家兔干眼病的症状。这些结果表明，所开发的粘膜粘附药物载体可以改善药物的递送，并具有治疗眼前部疾病的潜力。意义声明在本研究中，设计并构建了基于（3-aminomethylphenyl）boronic acid-conjugated chondroitin sulfate（APBA-ChS）的含地塞米松（DEX）的纳米结构脂质载体（NLC）。APBA-ChS存在于DEX-NLC表面，含有硼酸基团，可与眼粘蛋白中的唾液酸形成复合物，从而导致角膜前滞留时间延长。硼酸和唾液酸之间的这种亲和力用于开发粘膜粘附药物递送系统。开发的粘膜粘附药物载体表现出延长的保留时间和缓解干眼综合征。基于APBA-ChS的NLC可能被认为是一种很有前途的眼部给药系统，用于治疗眼前部疾病。
Dry eye syndrome is a common eye disease that affects many people worldwide. It is usually treated with eye drops, which has low bioavailability owing to rapid clearance from the ocular surface and leads to poor patient compliance and side effects. For the purpose of improving the therapeutic efficacy, nanostructured lipid carrier (NLC)-loaded dexamethasone (DEX) was prepared and functionalized with (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS). As APBA has a boronic acid group, it can form a high-affinity complex with sialic acids present in the ocular mucin, which contributes to extension of corneal retention time and improvement of drug delivery. Compared with eye drops, Rhodamine B (RhB)-labeled APBA-ChS-NLC could significantly prolong the residence time on the corneal surface. Moreover, the DEX-APBA-ChS-NLC showed no irritation to the rabbit eye as indicated in irritation studies and histological images. The pharmacodynamics study indicated that DEX-APBA-ChS-NLC could relieve symptoms of dry eye disease in rabbits. These results demonstrated that the developed mucoadhesive drug carrier could improve the delivery of drugs and have promising potential to treat anterior eye diseases.Statement of SignificanceIn this research, (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS)-based nanostructured lipid carriers (NLCs) including dexamethasone (DEX) were designed and constructed. APBA-ChS, which is present on the surface of DEX-NLC and contains the boronic acid group, can form complex with sialic acids in the ocular mucin, hence leading to prolonged precorneal retention. This affinity between boronic acid and sialic acids was used to develop a mucoadhesive drug delivery system. The developed mucoadhesive drug carrier demonstrated prolonged retention time and alleviation of dry eye syndrome. APBA-ChS-based NLC may be considered a promising ocular drug delivery system for treating anterior eye diseases.