Engineering a therapeutic solid lipid nanoparticle formulation of cannabidiol for treatment of COVID-19-Induced lung inflammation

设计用于治疗 COVID-19 引起的肺部炎症的大麻二酚治疗性固体脂质纳米颗粒制剂

• 批准号: 555158-2020
• 负责人: Allen, Christine
• 金额: $ 3.5万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=704946
• 关键词: Engineering; therapeutic; solid; lipid; nanoparticle

COVID-19 has been shown to result in an increased expression of certain cytokines (i.e. chemicals produced by the body in response to an infection that can result in inflammation) in patients, known as a "cytokine storm", which leads to organ and tissue damage. The cannabinoid, cannabidiol (CBD) has been shown to have anti-inflammatory activity in various animal models of disease. Of particular interest, CBD has been shown to reduce the expression of cytokines in models of lung inflammation. We hypothesize that the anti-inflammatory effect of CBD may offer some therapeutic benefit in patients with COVID-19 by reducing the levels of cytokines. There are specific challenges when administering CBD to patients. CBD is highly hydrophobic (i.e. difficult to dissolve in aqueous media) and is susceptible to degradation under a range of environmental conditions (including in the presence of light and oxygen). CBD is rapidly and extensively metabolized following oral administration. Additionally, inhalation (a common method for administering CBD) is undesirable in COVID-19 patients due to an increased likelihood of impaired lung function. In order to ensure that a therapeutic concentration of CBD reaches the bloodstream, we will formulate CBD into small particles comprised of lipids, called solid lipid nanoparticles (SLNs). These particles can be administered intranasally, a non-invasive method. In addition to improving the delivery of CBD, SLNs will protect CBD from degradation. Given that the SLN formulation will be designed using ingredients that are generally regarded as safe (GRAS) for human use, it will be straightforward to translate into the clinic. For this project, we will collaborate with a Canadian medical cannabis company, Avicanna Inc. Avicanna has expertise in scale-up and manufacturing of medical and pharmaceutical cannabinoid products and has worked with regulatory authorities to move products into clinical development. Bringing together the complementary expertise of the Allen Lab (i.e. drug delivery) and key members of Avicanna (i.e. scale-up, manufacturing and clinical development) will enable this project to move forward in an effective and timely manner.

COVID-19已显示导致某些细胞因子的表达增加（即，人体生产的化学物质是响应可能导致炎症的感染而产生的），该患者被称为“细胞因子风暴”，这会导致器官和组织损伤。大麻素，大麻二酚（CBD）已显示在各种疾病动物模型中具有抗炎活性。特别有趣的是，CBD已被证明可以减少肺部炎症模型中细胞因子的表达。我们假设CBD的抗炎作用可能通过降低细胞因子的水平来为COVID-19患者提供一些治疗益处。对患者进行CBD时会面临特定的挑战。 CBD是高度疏水的（即难以溶于水性培养基），并且在一系列环境条件下（包括在光和氧气的存在）下容易降解。口服后，CBD迅速和广泛代谢。另外，由于肺功能受损的可能性增加，因此在199例患者中，吸入（一种用于管理CBD的常见方法）是不良的。为了确保CBD的治疗浓度到达血液，我们将将CBD提出为由脂质组成的小颗粒，称为脂质脂质纳米颗粒（SLNS）。这些颗粒可以在鼻内施用，一种非侵入性方法。除了改善CBD的交付外，SLN还将保护CBD免受降解。鉴于SLN配方将使用通常被视为安全使用的成分（GRA）设计，因此可以简单地转化为诊所。对于这个项目，我们将与加拿大医疗大麻公司合作，Avicanna Inc. Avicanna在医疗和制药大麻素产品的扩大和制造方面具有专业知识，并与监管机构合作将产品转移到临床开发中。汇集了艾伦实验室（即药物输送）的互补专业知识和Avicanna的主要成员（即扩大，制造和临床开发）将使该项目能够有效，及时地前进。