Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, Maharashtra, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, Maharashtra, India.
Int J Pharm. 2020 Mar 15;577:119095. doi: 10.1016/j.ijpharm.2020.119095. Epub 2020 Jan 29.
The objective of the study was to assess the effect of enhanced mucoadhesion of a cationic mucoadhesive nanostructured lipid carrier (NLC) on its ocular disposition after topical administration. The NLC was made mucoadhesive by surface coating with chitosan oligosaccharide (COS), a low molecular weight derivate of chitosan which is more suitable for drug delivery applications as compared to the native chitosan. The NLC was characterised by surface evaluating techniques like SANS and XPS for confirming coating of COS over the surface of NLC. In order to assess the effect of COS coating on in vivo ocular mucoadhesion, coumarin loaded NLC were topically administered to rats and the sagittal sections of the eyes were imaged using confocal microscopy. The COS coated NLC were seen to adhere more around the ocular surface than the uncoated NLC during the 4-h study. The improved ocular retention for COS-NLC reflected on the content of Etoposide within the eye, which showed a higher concentration of Etoposide, as compared to the uncoated NLC. The NLC was also assessed for any ocular irritancy in rabbits and repeat dose toxicity in rats and found to be relatively non-irritant and non-toxic as compared to appropriate controls. Thus, the study asserts that to achieve higher concentration of therapeutics within the eye, the formulations like NLC are not just required to be permeating but also retentive on the surface of the eye to achieve appreciable concentrations.
本研究的目的是评估阳离子型黏膜黏附纳米结构化脂质载体 (NLC) 增强黏膜黏附性对其局部给药后眼部分布的影响。通过用壳聚糖寡糖 (COS) 对 NLC 进行表面涂层处理，使 NLC 具有黏膜黏附性，COS 是壳聚糖的低分子量衍生物，与天然壳聚糖相比，更适合药物输送应用。通过小角 X 射线散射 (SANS) 和 X 射线光电子能谱 (XPS) 等表面评估技术对 NLC 进行了表征，以确认 COS 涂覆在 NLC 表面。为了评估 COS 涂层对体内眼部黏膜黏附的影响，将香豆素负载的 NLC 局部施用于大鼠，并使用共聚焦显微镜对眼部的矢状切片进行成像。与未涂层的 NLC 相比，在 4 小时的研究过程中，COS 涂层的 NLC 被发现更能黏附在眼部周围。COS-NLC 的眼部保留时间的改善反映在眼内依托泊苷的含量上，与未涂层的 NLC 相比，眼内的依托泊苷浓度更高。还在兔子中评估了 NLC 的任何眼部刺激性，在大鼠中评估了重复剂量毒性，并发现与适当的对照相比，NLC 相对无刺激性和无毒。因此，该研究表明，为了在眼部达到更高的治疗药物浓度，像 NLC 这样的制剂不仅需要具有渗透性，还需要在眼部表面具有滞留性，以达到可观的浓度。
