Transport mechanism of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan decorated coumarin-6 loaded nanostructured lipid carriers across the rabbit ocular
Transport mechanism of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan decorated coumarin-6 loaded nanostructured lipid carriers across the rabbit ocular
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壳聚糖-N-乙酰半胱氨酸、壳寡糖或羧甲基壳聚糖修饰的香豆素-6负载纳米结构脂质载体穿过兔眼的转运机制
DOI：
10.1016/j.ejpb.2017.08.013
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发表时间：
2017
影响因子：
4.9
通讯作者：
Pan Weisan
中科院分区：
文献类型：
--
作者：
Li Jinyu;Tan Guoxin;Cheng Bingchao;Liu D;an;Pan Weisan
为了促进香豆素-6(Cou-6)模拟的疏水药物通过角膜进入兔眼前房，设计并表征了壳聚糖(CS)衍生物N-乙酰-L半胱氨酸(CS-NAC)、壳寡糖(COS)和羧甲基壳聚糖(CMCs)修饰的纳米结构脂质载体(NLCS)。在兔的活体大脑皮层滞留实验中，这些CS衍生物涂层显示出比Cou-6滴眼液和Cou-6-NLC更强的抗药性(P<0.05)，而且它们的AUC(0−∞)、Cmax和MRT(0−∞)遵循CMCS-Cou-6-NLC；Cos-Cou-6-NLC；Cos-Nac-Cou-6-NLC的顺序。激光共聚焦荧光显微镜在体外角膜穿透研究中发现，COS-和CS-NAC包裹的NLCs穿透整个角膜上皮屏障(约40μm)，而CMCs未能如预期的那样显著增强眼内药物的穿透，在30μm处显示出可忽略的荧光。此外，与CMCS-NLC相比，COS和CS-NAC涂层实现了对完整角膜的渗透，并彻底增加了对眼组织的渗透水平(P<0.05)，并成功地降低了结膜与角膜的渗透率(比率(C-S/C))，从而导致了更高的生物利用度，眼组织活体荧光成像证实了这一点。综上所述，CS-NAC-NLC和COS-NLC是一种很有前途的眼部给药系统，可以延长角膜前滞留时间、提高角膜渗透率和提高眼生物利用度。比较而言，CS-NAC-NLC具有最大的眼部给药潜力。
To facilitate the hydrophobic drugs modeled by coumarin-6 (Cou-6) acrossing the cornea to the anterior chamber of the rabbit eye, chitosan (CS) derivatives including chitosan-N-acetyl-l-cysteine (CS-NAC), chitosan oligosaccharides (COS) and carboxymethyl chitosan (CMCS) modified nanostructured lipid carriers (NLCs) were designed and characterized. We found that, with similar size distribution and positive charges, different CS derivatives based on NLCs led to distinctive delivery performance.In vivoprecorneal retention study on rabbits revealed that these CS derivatives coating exhibited a stronger resistant effect than Cou-6 eye drops and Cou-6-NLC (P < 0.05), moreover, the AUC(0−∞), Cmaxand MRT(0−∞)of them followed the sequence of CMCS-Cou-6-NLC < COS-Cou-6-NLC < CS-NAC-Cou-6-NLC. Confocal laser fluorescence microscopy (CLSM) forin vitrocorneal penetration study showed that COS-, and CS-NAC-coated NLCs penetrated through the whole corneal epithelium barrier (about 40 μm), while CMCS failed to significantly enhance the intraocular drug penetration as expected, displayed a negligible fluorescence at 30 μm deep. In addition, penetration through the intact cornea was achieved and the penetration levels through the ocular tissues were increased thoroughly for the COS and CS-NAC coating ones compared with CMCS-NLC (P < 0.05), and successfully reduced the conjunctival-to-corneal permeability ratio (ratio(C-S/C)) thus resulted in a higher bioavailability, which was confirmed byex vivofluorescence imaging on ocular tissues. In summary, CS-NAC-NLC and COS-NLC are promising ocular drug delivery systems to achieve prolonged precorneal retention, higher corneal permeability and enhanced ocular bioavailability. And comparatively speaking, CS-NAC-NLC possesses the highest potential for ocular drug delivery.