Precisely Engineered Biodegradable Intraocular Implants for the Sustained Release of Dexamethasone

Abstract

 

Purpose

 

The ability to fabricate biodegradable intraocular implants with uniform size, shape and dose for the sustained delivery of actives in multiple regions of the eye has proven elusive with current technologies. The acceptance of intravitreal implants for the localized treatment of multiple back-of-the-eye conditions have paved the way for the development of a new generation of smaller intraocular implants in the anatomically and clinically desirable, yet “hard-to-manufacture” size range of 100μm to 1,000μm. The ability to reproducibly fabricate implants in this size range opens up a window of opportunities for the injection and localization of implants against multiple target tissues of the inner eye where greater spatial constraints may exist.

 

Methods

 

We report the ability to precisely fabricate 150μm x 150μm x 500μm intraocular implants comprised of a blend of micronized dexamethasone and poly(lactic-co-glycolic) acid (PLGA) for the tunable release of active using the PRINT technology. Physicochemical characterization of the implants was performed to evaluate the overall mass uniformity range, dexamethasone content uniformity across individual implants, and the in-vitro release of dexamethasone from the implants in 1X PBS at 37°C.

 

Results

 

Liquidia’s PRINT technology unique ability to impart control over size and shape (Figure 1A) allowed for the fabrication of dexamethasone/PLGA implants (Figure 2A) with a high degree of mass uniformity (14μg, ±1μg) and dexamethasone content (2.2μg ±0.2μg). Furthermore, PRINT implants enabled for the sustained release of dexamethasone over therapeutically relevant timelines, with over 40% of the initial cargo retained in the implants after 35 days in 1X PBS at 37°C.

 

Conclusions

 

The PRINT technology uniquely allows for the fabrication of intraocular implants with uniform size, shape and dose. We demonstrated the ability to fabricate dexamethasone/PLGA intraocular implants in the desirable size range of 100μm to 1,000μm for sustained release applications where anatomical constraints may call for uniquely engineered implants.

 

 

Figure 1: A) SEM image of 150μm x 150μm x 500μm dexamethasone/PLGA PRNT intraocular implants, B) Close-up view of the implant’s surface, showing micronized dexamethasone embedded in PLGA matrix, C) In vitro dexamethasone release profile from PRINT implants over 35 days.

 

Keywords: 568 intraocular pressure • 607 nanotechnology • 608 nanomedicine