Université Paris Descartes, PRES Sorbonne Paris Cité, CNRS UMR 860, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologique, 45, Rue des Saints Peres, 75006, Paris, France; CQM - Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9020-105, Funchal, Portugal.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, PR China.
Eur J Med Chem. 2021 Jan 1;209:112905. doi: 10.1016/j.ejmech.2020.112905. Epub 2020 Oct 11.
There are several routes of administration to the brain, including intraparenchymal, intraventricular, and subarachnoid injections. The blood-brain barrier (BBB) impedes the permeation and access of most drugs to the central nervous system (CNS), and consequently, many neurological diseases remain undertreated. For past decades, to circumvent this effect, several nanocarriers have been developed to deliver drugs to the brain. Importantly, intranasal (IN) administration can allow direct delivery of drugs into the brain through the anatomical connection between the nasal cavity and brain without crossing the BBB. In this regard, dendrimers may possess great potential to deliver drugs to the brain by IN administration, bypassing the BBB and reducing systemic exposure and side effects, to treat diseases of the CNS. In this original concise review, we highlighted the few examples advocated regarding the use of dendrimers to deliver CNS drugs directly via IN. This review highlighed the few examples of the association of dendrimer encapsulating drugs (e.g., small compounds: haloperidol and paeonol; macromolecular compounds: dextran, insulin and calcitonin; and siRNA) using IN administration. Good efficiencies were observed. In addition, we will present the in vivo effects of PAMAM dendrimers after IN administration, globally, showing no general toxicity.
有几种向大脑给药的途径，包括脑实质内、脑室内和蛛网膜下腔注射。血脑屏障（BBB）阻碍了大多数药物向中枢神经系统（CNS）的渗透和进入，因此，许多神经疾病仍然治疗不足。过去几十年来，为了克服这一影响，已经开发了几种纳米载体将药物递送到大脑。重要的是，鼻内（IN）给药可以通过鼻腔和大脑之间的解剖连接直接将药物递送到大脑，而无需穿过 BBB。在这方面，树枝状聚合物通过 IN 给药将药物递送到大脑具有很大的潜力，可以绕过 BBB，减少全身暴露和副作用，从而治疗 CNS 疾病。在这篇原创的简明综述中，我们强调了几个提倡使用树枝状聚合物通过 IN 给药直接向大脑递药的例子。这篇综述强调了几种将药物包封在树枝状聚合物中的例子（例如，小分子：氟哌啶醇和丹皮酚；大分子化合物：葡聚糖、胰岛素和降钙素；和 siRNA）通过 IN 给药。观察到良好的效率。此外，我们将展示 PAMAM 树枝状聚合物在 IN 给药后的体内效应，总体上没有一般毒性。
