Suprachoroidal Delivery of Small Molecules, Nanoparticles, Gene and Cell Therapies for Ocular Diseases

Chen-Rei Wan, Leroy Muya, Viral Kansara, Thomas A Ciulla, Chen-Rei Wan, Leroy Muya, Viral Kansara, Thomas A Ciulla

Abstract

Suprachoroidal drug delivery technology has advanced rapidly and emerged as a promising administration route for a variety of therapeutic candidates, in order to target multiple ocular diseases, ranging from neovascular age-related macular degeneration to choroidal melanoma. This review summarizes the latest preclinical and clinical progress in suprachoroidal delivery of therapeutic agents, including small molecule suspensions, polymeric entrapped small molecules, gene therapy (viral and nonviral nanoparticles), viral nanoparticle conjugates (VNCs), and cell therapy. Formulation customization is critical in achieving favorable pharmacokinetics, and sustained drug release profiles have been repeatedly observed for multiple small molecule suspensions and polymeric formulations. Novel therapeutic agents such as viral and nonviral gene therapy, as well as VNCs, have demonstrated promise in animal studies. Several of these suprachoroidally-administered therapies have been assessed in clinical trials, including small molecule suspensions of triamcinolone acetonide and axitinib, viral vector RGX-314 for gene therapy, and VNC AU-011. With continued drug delivery research and optimization, coupled with customized drug formulations, suprachoroidal drug delivery may address large unmet therapeutic needs in ophthalmology, targeting affected tissues with novel therapies for efficacy benefits, compartmentalizing therapies away from unaffected tissues for safety benefits, and achieving durability to relieve the treatment burden noted with current agents.

Keywords: anti-VEGF; gene therapy; glaucoma; macular degeneration; microinjector; ocular drug delivery; suprachoroidal; suprachoroidal space (SCS).

Conflict of interest statement

C.W., L.M., V.K. and T.A.C. are all employees of Clearside Biomedical and own stocks from Clearside Biomedical.

Figures

Figure 1
Figure 1
Schematic of Microneedle Injection into the Suprachoroidal Space (SCS).
Figure 2
Figure 2
Modalities to Administer Therapeutic Agents into the Suprachoroidal Space (SCS).
Figure 3
Figure 3
Preclinical and Clinical Results of SC Administration of Small Molecule Suspensions. CLS-TA: investigational formulation of triamcinolone acetonide developed by Clearside Biomedical (Alpharetta, GA, USA); LPS: lipopolysaccharides.

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