Suprachoroidal delivery enables targeting, localization and durability of small molecule suspensions.

Drug delivery to the suprachoroidal space (SCS®) has become a clinical reality after the 2021 FDA approval of CLS-TA, a triamcinolone acetonide injectable suspension for suprachoroidal use (XIPERE®), administered via a microneedle-based device, the SCS Microinjector®. Suprachoroidal (SC) delivery facilitates targeting, compartmentalization, and durability of small molecule suspensions, thereby potentially addressing some of the efficacy, safety, and treatment burden limitations of current retinal therapies. Herein, the design features of the SCS Microinjector are reviewed, along with the biomechanics of SC drug delivery. Also presented are preclinical evaluations of SC small molecule suspensions from 4 different therapeutic classes (plasma kallikrein inhibitor, receptor tyrosine kinase inhibitor, corticosteroid, complement factor D inhibitor), highlighting their potential for durability, targeted compartmentalization, and acceptable safety profiles following microinjector-based SC delivery. The clinical evaluations of the safety, tolerability and efficacy of SC delivered triamcinolone further supports potential of SC small molecule suspensions as a clinically viable strategy for the treatment of chorioretinal diseases. Also highlighted are current limitations, key pharmacological considerations, and future opportunities to optimize the SC microinjector platform for safe, effective, and potentially long-acting drug delivery for the treatment of chorioretinal disorders.

Biomechanics of suprachoroidal drug delivery: From benchtop to clinical investigation in ocular therapies.

INTRODUCTION: 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.Areas covered: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. EXPERT OPINION: 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.