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.
Carbohydr Polym. 2016 Aug 1;146:435-44. doi: 10.1016/j.carbpol.2016.03.079. Epub 2016 Mar 29.
To develop a potential nanocarrier for the topical ocular administration of curcumin (CUR), a novel thiolated chitosan was synthesized by the covalent binding between N-acetyl-l-cysteine (NAC) and chitosan (CS) to surface modify the nanostructured lipid carrier loaded CUR (CUR-NLC). And the superiorities of the CS-NAC co polymer coated CUR-NLC over chitosan oligosaccharides (COS) or carboxymethyl chitosan (CMCS) modification were also verified in detail. As expected, the increment in particle size and the reversal of zeta potential occurred after surface decorating, and the most prominent electropositivity was obtained for the CS-NAC-CUR-NLC group. Additionally, the utilization of the CS-NAC coating demonstrated an effectively controlled release over 72h and attained a 6.4 and 18.8 fold increase in apparent permeability coefficients (Papp) compared with the CUR-NLC and the self-made eye drops, respectively. Meanwhile, the clearance rate of the NLC labeled with Rhodamine B was significantly delayed in the presence of CS-NAC. By contrast, CS-NAC-CUR-NLC was superior to the COS and CMCS coated ones in view of in vitro release, drug permeability and corneal retention. Moreover, the results of the in-vivo and in-vitro characteristics demonstrated that the promoting effect of CMCS coating was relatively weaker than COS coated ones. Ocular irritation test was executed on the CS-NAC-CUR-NLC, neither a sign of toxicity nor irritation to the external ocular tissues was observed. In conclusion, CS-NAC-CUR-NLC possesses a greater potential as an ocular drug-delivery system comparing with the COS-CUR-NLC and CMCS-CUR-NLC.
为了开发一种用于姜黄素（CUR）局部眼部给药的潜在纳米载体，通过 N-乙酰-L-半胱氨酸（NAC）与壳聚糖（CS）的共价结合，合成了一种新型巯基化壳聚糖，以表面修饰负载 CUR 的纳米结构脂质载体（CUR-NLC）。并且详细验证了 CS-NAC 共聚物修饰的 CUR-NLC 相对于壳寡糖（COS）或羧甲基壳聚糖（CMCS）修饰的优越性。不出所料，表面修饰后粒径增大，zeta 电位反转，CS-NAC-CUR-NLC 组获得最显著的正电性。此外，CS-NAC 涂层的利用可实现超过 72 小时的有效控制释放，并与 CUR-NLC 和自制滴眼剂相比，表观渗透系数（Papp）分别提高了 6.4 倍和 18.8 倍。同时，在 CS-NAC 存在的情况下，标记有 Rhodamine B 的 NLC 的清除率明显延迟。相比之下，在体外释放、药物渗透性和角膜滞留方面，CS-NAC-CUR-NLC 优于 COS 和 CMCS 涂层的 NLC。此外，体内和体外特性的结果表明，CMCS 涂层的促进作用比 COS 涂层的弱。在 CS-NAC-CUR-NLC 上进行了眼刺激性试验，未观察到对外眼部组织的毒性或刺激性迹象。总之，与 COS-CUR-NLC 和 CMCS-CUR-NLC 相比，CS-NAC-CUR-NLC 作为眼部药物传递系统具有更大的潜力。
