Controlled and Extended Release of Difluprednate from Biodegradable Intraocular Implants Engineered using PRINT® Technology

Abstract

 

Purpose

 

Intraocular biodegradable implants are a promising alternative for the treatment of several eye diseases through the control and extended release of active drugs. However, the ability to manufacture intraocular implants with controlled shape, size and drug dose for sustained active delivery has been limited with current technologies. Such a capability will pave the way for effective treatment of many ophthalmic conditions by localization of implants and controlled release of actives near target eye tissues. Here, we present the reproducible fabrication and sustained release of difluprednate from biodegradable implants at a relevant implant size, drug dose and release rates using Envisia’s proprietary PRINT technology.

 

Methods

 

We fabricated 225μm x 225μm x 4000μm intraocular implants comprised of a blend of micronized difluprednate and biodegradable polymers including poly(caprolactone) and poly(lactic-co-glycolic) acid (PLGA) to tune the release of active using the PRINT technology. Overall mass uniformity and difluprednate content uniformity across individual implants were evaluated. The in-vitro release of difluprednate from the implants was evaluated in 1X PBS + 1% SDS at 37°C.

 

Results

 

Envisia’s PRINT technology has the unique ability to impart control over size and shape which allows for the fabrication of difluprednate/PLGA implants (Figure 1A) with a high degree of mass uniformity (211μg, ±4 μg) and difluprednate content (60μg ±1.8μg). PRINT implants enable the extended release of difluprednate over therapeutically relevant timelines when evaluated in vitro (Figure 1B). Modulation of the formulation composition allows for tuning of the active release profile from 20% release up to >80% release after 20 days in 1X PBS + 1% SDS at 37°C.

 

Conclusions

 

The ability to fabricate difluprednate/PLGA intraocular implants in the desirable size range was demonstrated. Tunable active release profiles of the hydrophobic steroid difluprednate in vitro were observed thus allowing further development of the extended release therapy for treatment of ocular inflammation and pain.

 

 

Figure 1: A) SEM image of 225μm x 225μm x 4000μm difluprednate/PLGA PRINT intraocular implants and B) In vitro difluprednate release profile from four PRINT implant formulations over 20 days with tunable drug release profiles.

 

Keywords: 557 inflammation • 487 corticosteroids • 607 nanotechnology