Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome.

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.