Precisely Engineered Biodegradable Drug Delivery Systems for the Extended Release of Prostaglandin Analogues in the Anterior Chamber

Abstract

 

Purpose

 

Biodegradable intraocular implants are one of the most attractive alternatives to achieve extended release of actives in the eye, bypassing issues associated with patient non-compliance and significantly improving therapeutic and safety profiles. However, the ability to precisely fabricate intracameral implants for the extended release of prostaglandin analogues (PGAs) in the anterior chamber with reproducible size, shape and dose has proven elusive with current technologies (i.e. hot-melt extrusion, in-situ gelation). The ability to reproducibly fabricate implants in the 100 μm to 3,000 μm size range enables for simple insertion and anatomically compatible placement of PGA drug delivery systems at the iridocorneal angle for the sustained reduction of elevated intraocular pressure in patients with glaucoma.

 

Methods

 

We report the ability to precisely fabricate intraocular implants comprised of a blend of PGA, polylactic acid (PLA) and/or poly(lactic-co-glycolic) acid (PLGA) for the tunable release of actives using the PRINT® (Particle Replication in Non-wetting Templates) technology. PGA dose content uniformity and in-vitro release of PGA from the implants in physiologically relevant media at 37°C over time were evaluated.

 

Results

 

Envisia’s PRINT micromolding technology uses templates (Figure 1A) to fabricate PGA/PLA/PLGA implants with precise and anatomically relevant size and shape (Figure 1B, Figure 1C and Figure 1D). Implants with low PGA doses and high degree of dose content uniformity (10.6 μg, ±0.5 μg) were achieved. Moreover, the technology offers the ability to formulate implants with tunable release profiles over therapeutically relevant timelines in-vitro, from a few weeks to several months (Figure 1E).

 

Conclusions

 

The PRINT technology uniquely allows for the fabrication of intracameral implants with uniform size, shape and dose. We demonstrated the ability to fabricate PGA/PLA/PLGA intracameral implants in the desirable size range of 100 μm to 3,000 μm for extended release of PGA where anatomical constraints may call for uniquely engineered implants.

 

 

Figure 1: PRINT Technology: A) mold template, B) implants on array, C) implant in needle, D) size comparison between two PRINT implants and a dime, E) in-vitro release of PGA from PRINT implants with durations of action from weeks to several months.

 

Keywords: 568 intraocular pressure • 420 anterior chamber