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

ABSTRACT

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.

KEYWORDS:

• Age-related macular degeneration
• diabetic macula edema
• gene Therapy
• microneedle
• ocular Drug delivery
• ocular melanoma
• retinal vein occlusion
• scs
• suprachoroidal
• uveitis

Article highlights

• The suprachoroidal space (SCS) is a potential space in the eye, opened by drug candidate injection, between the sclera and the choroid tissue layers.

• Injected fluids spread circumferentially and posteriorly within the SCS, targeting chorio-retinal tissues to potentially maximize efficacy, while compartmentalizing therapies away from the unaffected vitreous and anterior segment to potentially enhance safety.

• Microneedle delivery to the SCS can be accomplished in an office-based, non-surgical setting by a physician trained in the suprachoroidal injection technique.

• Delivery to the SCS via microneedles has been shown to be safe and effective preclinically and clinically in a Phase 3 trial of CLS-TA, a proprietary investigational suspension of triamcinolone acetonide.

• Suspension formulations with low solubility exhibit sustained pharmacokinetics in the SCS, demonstrated by the clinical trials involving the use of suprachoroidally injected CLS-TA.

• Drug formulations can be tailored to the desired target product profile. Physical and fluidic properties of injectates into the SCS, including volume, viscosity, particle size, and injection pressure, can impact the spread and extent of opening of the SCS. For instance, drug spread is directly proportional to the injected volume and inversely proportional to the viscosity.

This box summarizes key points contained in the article.

List of abbreviations

SCS,	=	Suprachoroidal Space
PK,	=	Pharmacokinetic
CLS-TA,	=	Investigational formulation, triamcinolone acetonide
IOP,	=	Intraocular pressure
UBM,	=	Ultrasound biomicroscopy
OCT,	=	Optical coherence tomography
HBSS,	=	Hank’s Balanced Salt Solution
CMC,Carboxymethyl cellulose	=
PLGA,	=	Poly(lacto-co-glyolic acid)
ACF,	=	Acriflavine
CNV,	=	Choroidal neovascularization
MW,	=	Molecular weight
HA,	=	Hyaluronic acid
RPE,	=	Retinal pigment epithelium
CST,	=	Central subfield retinal thickness
SD-OCT,	=	Spectral-domain OCT
AS-OCT,	=	Anterior segment OCT.

Declaration of interest

SE Hancock, TA Ciulla, CR Wan, NE Fisher, RV Andino are employees of, and hold stock option with, Clearside Biomedical, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Clearside Biomedical, Inc.