用于递送至眼后段组织的吲哚美辛局部眼用脂质纳米颗粒制剂（固体脂质纳米粒、纳米结构脂质载体）

Topical ophthalmic lipid nanoparticle formulations (SLN, NLC) of indomethacin for delivery to the posterior segment ocular tissues.

作者信息

Balguri Sai Prachetan, Adelli Goutham R, Majumdar Soumyajit

机构信息

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, United States.

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, United States; Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, United States.

出版信息

Eur J Pharm Biopharm. 2016 Dec;109:224-235. doi: 10.1016/j.ejpb.2016.10.015. Epub 2016 Oct 25.

DOI:10.1016/j.ejpb.2016.10.015

PMID:27793755

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5345266/

Abstract

PURPOSE

The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery.

METHODS

IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt.<200kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies.

RESULTS

For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226±5, 265±8, and 227±11nm, respectively; the zeta potential was -22±0.8, 27±1.2, and -12.2±2.3mV, respectively; the polydispersity index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81±0.9, 91.5±3.2 and 99.8±0.2%, respectively. The surface modification of the SLNs with CS increased the ocular penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo.

CONCLUSION

The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery to anterior and posterior segment ocular tissues.

摘要

目的

本研究的目的是制备载有吲哚美辛（IN）的固体脂质纳米粒（SLNs）和纳米结构脂质载体（NLCs），并研究它们在眼部局部给药中的潜在用途。

方法

制备、表征并评估了IN SLNs（0.1% w/v）和NLCs（0.8% w/v）。评估了它们在角膜和巩膜-脉络膜-视网膜色素上皮（跨SCR）组织中的体外释放和通量概况以及体内眼部组织分布。此外，使用阳离子水溶性渗透促进剂氯化壳聚糖（CS）（分子量<200kDa）对SLNs的表面进行修饰，并通过体外跨膜渗透和体内分布组织研究来研究其效果。

结果

对于IN-SLNs、IN-CS-SLNs和IN-NLCs，粒径分别为226±5、265±8和227±11nm；zeta电位分别为-22±0.8、27±1.2和-12.2±2.3mV；多分散指数（PDI）分别为0.17、0.30和0.23；包封率（EE）分别为81±0.9、91.5±3.2和99.8±0.2%。用CS对SLNs进行表面修饰增加了IN的眼部渗透。与体内评估的其他制剂相比，NLCs在所有测试的眼部组织中保持明显更高的IN浓度。