I. Alquisiras-Burgos, Irma Gabriela González-Herrera, Sergio Alcalá-Alcalá, P. Aguilera
{"title":"Nose-to Brain Delivery of Resveratrol, a Non-Invasive Method for the Treatment of Cerebral Ischemia","authors":"I. Alquisiras-Burgos, Irma Gabriela González-Herrera, Sergio Alcalá-Alcalá, P. Aguilera","doi":"10.3390/ddc3010007","DOIUrl":null,"url":null,"abstract":"Cerebral ischemia represents a particular condition among neurological diseases due to its high frequency, high associated mortality, and the permanent disability in patients that survive it. Numerous studies in animal models have demonstrated the protective properties of resveratrol against cerebral ischemia. Resveratrol is a soluble molecule in polar solvents with high membrane permeability; however, it is rapidly metabolized at the liver and is also a substrate of the ATP binding cassette transporters located at the blood–brain barrier. These circumstances reduced bioavailability of resveratrol to the brain. In this review, we examined nasal resveratrol’s formulations including nanocarriers such as nanostructured lipid carriers, nanoemulsions, nanoparticles, bilosomes, cubosomal, and transferosomes that are directly transported to the brain. An intranasal administration route evades resveratrol transformation due to liver metabolism. Components of nanoformulations increased resveratrol absorption to the brain by enhancing permeation through specific approaches and also maintaining stability during storage. Both characteristics improved the delivery of resveratrol with conserved antioxidant capacity and protective properties for neurological models. Although demonstration that the nanoformulations prevents resveratrol’s blood–brain barrier retention is missing, properties of resveratrol’s nanoformulation encourage testing in clinical trials; however, regulatory approval for a novel nanocarrier in nasal drug delivery is complicated and needs approval.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"80 8","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drugs and Drug Candidates","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/ddc3010007","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Cerebral ischemia represents a particular condition among neurological diseases due to its high frequency, high associated mortality, and the permanent disability in patients that survive it. Numerous studies in animal models have demonstrated the protective properties of resveratrol against cerebral ischemia. Resveratrol is a soluble molecule in polar solvents with high membrane permeability; however, it is rapidly metabolized at the liver and is also a substrate of the ATP binding cassette transporters located at the blood–brain barrier. These circumstances reduced bioavailability of resveratrol to the brain. In this review, we examined nasal resveratrol’s formulations including nanocarriers such as nanostructured lipid carriers, nanoemulsions, nanoparticles, bilosomes, cubosomal, and transferosomes that are directly transported to the brain. An intranasal administration route evades resveratrol transformation due to liver metabolism. Components of nanoformulations increased resveratrol absorption to the brain by enhancing permeation through specific approaches and also maintaining stability during storage. Both characteristics improved the delivery of resveratrol with conserved antioxidant capacity and protective properties for neurological models. Although demonstration that the nanoformulations prevents resveratrol’s blood–brain barrier retention is missing, properties of resveratrol’s nanoformulation encourage testing in clinical trials; however, regulatory approval for a novel nanocarrier in nasal drug delivery is complicated and needs approval.
脑缺血是神经系统疾病中的一种特殊情况,因为其发病率高、相关死亡率高,而且存活下来的患者会终身残疾。大量动物模型研究表明,白藜芦醇对脑缺血具有保护作用。白藜芦醇是一种可溶于极性溶剂的分子,具有很高的膜渗透性;但它在肝脏中会迅速代谢,而且还是位于血脑屏障的 ATP 结合盒转运体的底物。这些情况降低了白藜芦醇在大脑中的生物利用率。在这篇综述中,我们研究了白藜芦醇的鼻腔给药配方,包括纳米载体,如纳米结构脂质载体、纳米乳剂、纳米颗粒、双体、立方体和转运体等,这些载体可直接转运到大脑。鼻内给药途径可避免白藜芦醇因肝脏代谢而发生转化。纳米制剂的成分可通过特定途径增强渗透性,并在储存过程中保持稳定,从而增加大脑对白藜芦醇的吸收。这两种特性改善了白藜芦醇的输送,并保持了其抗氧化能力和对神经模型的保护特性。虽然还没有证明纳米制剂能防止白藜芦醇在血脑屏障中的滞留,但白藜芦醇纳米制剂的特性鼓励在临床试验中进行测试;然而,鼻腔给药中的新型纳米载体需要复杂的监管审批。