基于结冷胶的那他霉素传递体转化系统改善了局部眼用递药。
Gellan Gum Based Transforming System of Natamycin Transfersomes Improves Topical Ocular Delivery.
机构信息
Department of Pharmaceutics and Drug Delivery, School of Pharmacy (K.Y.J., A.T., N.D., S.P.B., S.M.), and Research Institute of Pharmaceutical Sciences (S.M.), University of Mississippi, Oxford, Mississippi; Department of Ophthalmology, University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, Tennessee (M.M.I., D.N.M., M.M.J.); and Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt (M.M.I., D.N.M.).
Department of Pharmaceutics and Drug Delivery, School of Pharmacy (K.Y.J., A.T., N.D., S.P.B., S.M.), and Research Institute of Pharmaceutical Sciences (S.M.), University of Mississippi, Oxford, Mississippi; Department of Ophthalmology, University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, Tennessee (M.M.I., D.N.M., M.M.J.); and Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt (M.M.I., D.N.M.)
出版信息
J Pharmacol Exp Ther. 2019 Sep;370(3):814-822. doi: 10.1124/jpet.119.256446. Epub 2019 Mar 14.
Short precorneal residence time and poor transocular membrane permeability are the major challenges associated with topical ocular drug delivery. In the present research, the efficiency of the electrolyte-triggered sol-to-gel-forming system of natamycin (NT) transfersomes was investigated for enhanced and prolonged ophthalmic delivery. Transfersomes were optimized by varying the molar ratios of phospholipid, sorbitan monostearate (Span) and tocopheryl polyethylene glycol succinate (TPGS). NT transfersome formulations (FNs) prepared with a 1:1 molar ratio of phospholipid-to-Span and low levels of TPGS showed optimal morphometric properties, and were thus selected to fabricate the in situ gelling system. Gellan gum-based (0.3% w/v) FN-loaded formulations (FNGs) immediately formed an in situ gel in the simulated tear fluid, with considerable viscoelastic characteristics. In vitro cytotoxicity in corneal epithelial cells and corneal histology studies demonstrated the ocular safety and cytocompatibility of these optimized formulations. Transcorneal permeability of NT from these formulations was significantly higher than in the control suspension. Moreover, the ocular disposition studies of NT, from the FNs and FNGs, in New Zealand male albino rabbits demonstrated the superiority of the electrolyte-sensitive FNGs in terms of NT delivery to the ocular tissues.
短的角膜前停留时间和差的跨眼部膜通透性是与局部眼部药物递送相关的主要挑战。在本研究中，考察了纳他霉素（NT）传递体的电解质触发溶胶-凝胶形成系统的效率，以增强和延长眼部递药。通过改变磷脂、山梨醇单硬脂酸酯（Span）和生育酚聚乙二醇琥珀酸酯（TPGS）的摩尔比来优化传递体。用磷脂与 Span 的摩尔比为 1:1 以及低水平的 TPGS 制备的 NT 传递体配方（FNs）显示出最佳的形态学特性，因此被选择来制备原位凝胶系统。基于结冷胶的（0.3%w/v）FN 负载配方（FNGs）在模拟泪液中立即形成原位凝胶，具有相当大的粘弹性。角膜上皮细胞的体外细胞毒性和角膜组织学研究表明这些优化配方具有眼部安全性和细胞相容性。这些制剂中 NT 的跨角膜透过性明显高于对照混悬液。此外，在新西兰雄性白化兔中，从 FNs 和 FNGs 进行的 NT 眼内分布研究表明，在向眼部组织递送 NT 方面，电解质敏感的 FNGs 具有优越性。
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