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

COVID-19已被证明会导致患者体内某些细胞因子（即身体响应感染而产生的化学物质，可导致炎症）的表达增加，称为“细胞因子风暴”，导致器官和组织损伤。大麻素，大麻二酚（CBD）已被证明在各种疾病的动物模型中具有抗炎活性。特别令人感兴趣的是，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水平为COVID-19患者提供一些治疗益处。在向患者施用CBD时存在特定的挑战。CBD是高度疏水性的（即难以溶解在水性介质中），并且在一系列环境条件下（包括在光和氧气的存在下）易于降解。CBD在口服给药后迅速而广泛地代谢。此外，由于肺功能受损的可能性增加，吸入（施用CBD的常用方法）在COVID-19患者中是不期望的。为了确保CBD的治疗浓度到达血液，我们将CBD配制成由脂质组成的小颗粒，称为固体脂质纳米颗粒（SLN）。这些颗粒可以鼻内给药，这是一种非侵入性方法。除了改善CBD的输送外，SLN还将保护CBD免受降解。鉴于SLN制剂将使用通常被认为对人类使用安全（GRAS）的成分进行设计，因此将其直接转化为临床。在这个项目中，我们将与加拿大医用大麻公司Avicanna Inc.合作。Avicanna在扩大和制造医疗和药用大麻素产品方面拥有专业知识，并与监管机构合作，将产品投入临床开发。汇集艾伦实验室（即药物输送）和Avicanna关键成员（即规模扩大，制造和临床开发）的互补专业知识将使该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.