Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication
Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication
复制标题
DOI：
10.1016/j.ijpharm.2018.12.015
复制
发表时间：
2019-02-10
影响因子：
5.8
通讯作者：
Metwally, Abdelkader A.
中科院分区：
文献类型：
--
作者：
Hathout, Rania M.;Gad, Heba A.;Metwally, Abdelkader A.
使用眼部药物治疗青光眼需要克服角膜对药物渗透的障碍。脂质体具有较强的角膜穿透能力和亲和力，但稳定性差，亲水性药物包封率低，药物释放快。本工作旨在开发一种新的、有效的、稳定的、具有缓释性能的青光眼药物-马来酸替莫洛胶化核心脂质体。采用完全析因设计研究了三个处方变量对载药量和囊泡大小的影响。采用薄膜水合法制备了微囊，并对其体外释药性能和稳定性进行了表征。对青光眼兔眼进行了体内眼压降低的评价。安全性通过组织病理学检查进行评估。明胶显著提高了药物的包封率，包封率达50%，粒径为38.81微米。与市售产品和传统脂质体相比，明胶具有明显的缓释作用。随着安全的组织学发现，制备的囊泡引起了最高的眼压下降。本工作提供了一种安全有效的新型眼部青光眼用药--马来酸替莫洛尔凝胶化核心脂质体，解决了亲水性药物眼部脂质体制剂的主要问题，适用于制药行业，含有丰富而相对廉价的成分。
Glaucoma treatment with ocular medications requires overcoming the corneal barrier to drug penetration. Liposomes have a great corneal penetration ability and affinity while suffering from poor stability and low entrapment of hydrophilic drugs accompanied by rapid drug release. This work aims to develop a new, effective and stable glaucoma medication with sustained drug release properties; Timolol maleate gelatinized core liposomes. A full factorial design was utilized to study the effects of three formulation variables on drug loading and vesicle particle size. Vesicles were prepared by the thin-film hydration method, and characterized for in-vitro drug release and stability. Intra-ocular pressure (IOP) reduction was evaluated in-vivo on glaucomatous rabbit's eyes. The safety profile was assessed using histopathological examinations. Gelatin significantly increased the drug entrapment percentage reaching 50% with a particle size of 38.81 mu m. Sustained drug release was recorded compared to a marketed product and to a conventional liposomal formulation. The prepared vesicles caused the highest reduction in IOP accompanied by safe histological findings. This work provided a new, safe and effective ocular glaucoma medication; Timolol maleate gelatinized core liposomes, solving the main problems of ocular liposomal formulations of hydrophilic drugs, suitable for the pharmaceutical industry and comprising abundant and relatively cheap components.