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

新冠肺炎已被证明会导致患者体内某些细胞因子(即身体对可能导致炎症的感染产生的化学物质)的表达增加，这被称为“细胞因子风暴”，从而导致器官和组织损伤。大麻素，大麻二醇(CBD)已被证明在各种疾病动物模型中具有抗炎活性。特别有趣的是，CBD已被证明在肺部炎症模型中减少细胞因子的表达。我们推测，CBD的抗炎作用可能通过降低细胞因子水平为新冠肺炎患者提供一定的治疗益处。当给患者使用CBD时，存在特定的挑战。CBD是高度疏水的(即很难溶解在水介质中)，在一系列环境条件下(包括在光和氧气存在的情况下)容易降解。CBD在口服后代谢迅速且广泛。此外，吸入(一种常见的给药方法)对于新冠肺炎患者是不可取的，因为肺功能受损的可能性增加。为了确保CBD的治疗浓度到达血流，我们将CBD制成由脂质组成的小颗粒，称为固体脂质纳米粒(SLN)。这些微粒可以鼻腔给药，这是一种非侵入性的方法。除了改善CBD的交付，SLNS还将保护CBD不被降解。考虑到SLN配方将使用通常被认为对人类安全的成分(GRAS)设计，它将直接转化为临床。对于这个项目，我们将与加拿大医用大麻公司Avicanna Inc.合作。Avicanna在医疗和药物大麻产品的扩大和制造方面拥有专业知识，并与监管机构合作，将产品应用于临床开发。将艾伦实验室的互补专业知识(即药物输送)和Avicanna的主要成员(即扩大规模、制造和临床开发)结合在一起，将使这一项目能够有效和及时地向前推进。

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.