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黏膜纳米粒子:毒理学概述。

Transmucosal Nanoparticles: Toxicological Overview.

机构信息

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.

Department of Pharmacology and Toxicology, Bombay College of Pharmacy, Mumbai, India.

出版信息

Adv Exp Med Biol. 2018;1048:37-57. doi: 10.1007/978-3-319-72041-8_3.

Abstract

Nanoparticles have specific physicochemical properties different to bulk materials of the same composition and such properties make them very attractive for commercial and medical applications. Mucoadhesive nanoparticulate dosage forms are designed to enable prolonged retention of these nanoparticles at the site of application, providing a controlled drug release for improved therapeutic outcome. Moreover, drug delivery across the mucosa bypasses the first-pass hepatic metabolism and avoids the degradation by gastrointestinal enzymes. However, like most new technologies, there is a rising debate concerning the possible transmucosal side effects resulting from the use of particles at the nano level. In fact, these nanoparticles on entering the body, deposit in several organs and may cause adverse biological reactions by modifying the physiochemical properties of living matter. Several investigators have found nanoparticles responsible for toxicity in different organs. In addition, the toxicity of nanoparticles also depends on whether they are persistent or cleared from the different organs of entry and whether the host can raise an effective response to sequester or dispose of the particles. In contrast to many efforts aimed at exploiting desirable properties of nanoparticles for medicine, there are limited attempts to evaluate potentially undesirable effects of these particles when administered intentionally for medical purposes. This chapter focuses on the overview of the mucosal systems, fate of nanoparticles, mechanism of nanoparticle's toxicity and the various toxicity issues associated with nanoparticles through mucosal routes.

摘要

纳米颗粒具有不同于相同组成的体材料的特定物理化学性质,这些性质使它们非常适合商业和医疗应用。黏附纳米颗粒剂型旨在使这些纳米颗粒在应用部位的停留时间延长,提供受控的药物释放,从而改善治疗效果。此外,药物通过黏膜的传递绕过了首过肝代谢,并避免了胃肠道酶的降解。然而,与大多数新技术一样,人们对使用纳米级颗粒可能产生的跨黏膜副作用存在争议。事实上,这些纳米颗粒进入人体后,会在几个器官中沉积,并可能通过改变生物物质的物理化学性质而引起不良反应。一些研究人员发现,纳米颗粒会导致不同器官的毒性。此外,纳米颗粒的毒性还取决于它们是否在进入的不同器官中持续存在或被清除,以及宿主是否能够对这些颗粒进行有效的隔离或处理。与许多旨在利用纳米颗粒在医学上的理想特性的努力不同,对于这些颗粒在出于医疗目的有意给药时可能产生的不良影响,评估的尝试有限。本章重点介绍黏膜系统概述、纳米颗粒的命运、纳米颗粒毒性的机制以及通过黏膜途径与纳米颗粒相关的各种毒性问题。

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