纳米乳载体用于药物递送:环境危害评估。

Nanoemulsion carriers for drug delivery: Assessment of environmental hazards.

机构信息

Department of Biology & CESAM, University of Aveiro, 3810-193, Aveiro, Portugal.

Nanovector srl, Via livorno, 60, 10144, Torino, TO, Italy.

出版信息

Environ Pollut. 2023 Jul 1;328:121669. doi: 10.1016/j.envpol.2023.121669. Epub 2023 Apr 18.

Abstract

Nanoemulsions (NEs) have been extensively studied as carriers for drug delivery, since these provide a good alternative to the existing non-nano systems, while promoting their target delivery and controlled release. NEs are considered safe drug carriers from a pre-clinical perspective, but there is currently no information on their ecotoxicological effects. In the present study we investigated the toxicity of a NE material (lecithin, sunflower oil, borate buffer) designed to be used as a liposomal excipient for eye drops, further referred to as (Lipid Particle:LP) LP_Eye and its dispersant (borate buffer) (LP_Eye disp.). Effects were assessed using two model species in soil ecotoxicology in LUFA 2.2 soil: Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola), based on the OECD standard guideline (28 days) and its extension, a longer-term exposure (56 days). The endpoints evaluated included survival, reproduction, and size. LP_Eye and LP_Eye disp. were toxic to E. crypticus and F. candida, affecting all measured endpoints. The toxicity of LP_Eye in E. crypticus seemed to be induced by the dispersant, whereas for F. candida, more sensitive, this was less explanatory. There were no indications that toxicity increased with longer exposure. Current results provide ecotoxicological data for a group of NMs that was absent, revealing toxicity to relevant environmental species. Indications were that the dispersant contributed to most of the observed effects, thus there is room to improve the formulation and achieve lower environmental impact.

摘要

纳米乳剂 (NEs) 已被广泛研究作为药物传递载体,因为它们为现有的非纳米系统提供了一个很好的替代方案,同时促进了它们的靶向传递和控制释放。从临床前角度来看,NEs 被认为是安全的药物载体,但目前尚无关于其生态毒理学效应的信息。在本研究中,我们研究了一种设计用于滴眼剂的脂质体赋形剂的 NE 材料(卵磷脂、葵花籽油、硼酸盐缓冲液)的毒性,进一步称为(脂质颗粒:LP)LP_Eye 及其分散剂(硼酸盐缓冲液)(LP_Eye disp.)。使用土壤生态毒理学中的两种模式物种(Enchytraeus crypticus(寡毛纲)和 Folsomia candida(弹尾目))在 LUFA 2.2 土壤中根据 OECD 标准指南(28 天)及其扩展进行了评估,暴露时间更长(56 天)。评估的终点包括存活、繁殖和大小。LP_Eye 和 LP_Eye disp. 对 E. crypticus 和 F. candida 均具有毒性,影响所有测量的终点。LP_Eye 在 E. crypticus 中的毒性似乎是由分散剂引起的,而对于更敏感的 F. candida,则不太具有解释性。没有迹象表明毒性随暴露时间的延长而增加。目前的结果为一组缺乏生态毒理学数据的 NM 提供了生态毒理学数据,揭示了对相关环境物种的毒性。结果表明,分散剂导致了大部分观察到的效应,因此有改进配方和降低环境影响的空间。

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