Clearside Biomedical Inc., Alpharetta, GA USA.
Expert Opin Drug Deliv. 2021 Jun;18(6):777-788. doi: 10.1080/17425247.2021.1867532. Epub 2021 Jan 3.
As research in suprachoroidal drug delivery advances, and therapeutic candidates, ranging from small molecule suspensions to gene therapy, progress through clinical trials, an understanding of suprachoroidal space (SCS) biomechanics assumes increasing importance.Numerous anatomic features play an important role in therapeutic access to the SCS. Methods of access include a catheter, a standard hypodermic needle, and a microinjector with microneedle. Physical and fluidic properties of injectates into the SCS, such as volume, viscosity, particle size, osmotic pressure, and ionic charge of formulation can impact the spread and extent of opening of the SCS. Pharmacokinetic data of several small molecule suspensions yielded favorable ocular distribution and pharmacokinetic profiles. Phase 2 and 3 clinical trials have been completed with a suprachoroidally injected corticosteroid; results and information on procedural details with the microinjector are discussed.
Suprachoroidal drug delivery has been demonstrated to be a reliable and consistent drug delivery method for targeted treatment of retinal and choroidal disorders to potentially maximize efficacy, while compartmentalizing therapies away from the unaffected tissues to potentially enhance safety. These delivery attributes, along with fluid transport properties and formula customization for pharmacological agents, may allow for more tailored treatment of diseases affecting chorio-retinal tissues.
随着巩膜下药物输送研究的进展，以及从小分子混悬剂到基因治疗等治疗候选药物在临床试验中取得进展，对巩膜下间隙（SCS）生物力学的理解变得越来越重要。许多解剖学特征对治疗性进入 SCS 起着重要作用。进入 SCS 的方法包括导管、标准皮下注射器和带有微针的微注射器。注入 SCS 的注入物的物理和流体特性，如体积、粘度、粒径、渗透压和配方的离子电荷，会影响 SCS 的扩散和开放程度。几种小分子混悬剂的药代动力学数据显示出良好的眼部分布和药代动力学特征。一种巩膜下注射的皮质类固醇已经完成了 2 期和 3 期临床试验；讨论了使用微注射器的结果和程序细节信息。
巩膜下药物输送已被证明是一种可靠且一致的药物输送方法，可用于靶向治疗视网膜和脉络膜疾病，从而有可能最大限度地提高疗效，同时将治疗药物与未受影响的组织隔离开来，从而有可能提高安全性。这些输送特性，以及用于药理学制剂的流体输送特性和配方定制，可能允许更针对影响脉络膜组织的疾病进行治疗。
