School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
Acta Biomater. 2019 Nov;99:350-362. doi: 10.1016/j.actbio.2019.08.035. Epub 2019 Aug 23.
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 SIGNIFICANCE: In 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.
干眼症是一种常见的眼病，影响着全球许多人。它通常通过眼药水治疗，但由于在眼表面迅速清除，导致生物利用度低，从而导致患者的依从性差和副作用。为了提高治疗效果，制备了负载地塞米松（DEX）的纳米结构化脂质载体（NLC），并用（3-氨甲基苯基）硼酸偶联的硫酸软骨素（APBA-ChS）进行功能化。由于 APBA 具有硼酸基团，它可以与眼部粘液中的唾液酸形成高亲和力的复合物，这有助于延长角膜滞留时间并改善药物传递。与眼药水相比，罗丹明 B（RhB）标记的 APBA-ChS-NLC 可以显著延长在角膜表面的停留时间。此外，在刺激性研究和组织学图像中，DEX-APBA-ChS-NLC 对兔眼没有刺激性。药效学研究表明，DEX-APBA-ChS-NLC 可以缓解兔干眼症的症状。这些结果表明，开发的粘膜粘附性药物载体可以改善药物的传递，并具有治疗前眼部疾病的潜在前景。 意义声明：在这项研究中，设计并构建了基于（3-氨甲基苯基）硼酸偶联的硫酸软骨素（APBA-ChS）的纳米结构化脂质载体（NLC），其中包含地塞米松（DEX）。APBA-ChS 存在于 DEX-NLC 的表面上，并且含有硼酸基团，可以与眼部粘液中的唾液酸形成复合物，从而导致前角膜滞留时间延长。硼酸和唾液酸之间的这种亲和力被用于开发粘膜粘附性药物传递系统。开发的粘膜粘附性药物载体表现出延长的保留时间和缓解干眼症。基于 APBA-ChS 的 NLC 可被视为治疗前眼部疾病的有前途的眼部药物传递系统。
