In vitro and In vivo Sustained Release of Dexamethasone from a PRINT Microparticle Suspension

Abstract

Purpose : Intravitreal delivery of dexamethasone is used in the treatment of diabetic macular edema (DME), retinal vein occlusion (RVO), and uveitis. Here we demonstrate sustained release of dexamethasone both in vitro and in vivo in the rabbit vitreous using microparticles fabricated using PRINT technology. PRINT microparticles have highly uniform shape, size and drug loading for more reproducible release rates and can be injected at high concentrations allowing for large drug doses using small needle gauge sizes.

Methods : Microparticles were analyzed for morphology by scanning electron microscopy (SEM) and for dexamethasone content by HPLC. In vitro release was monitored in PBS pH 7.2 at 37°C and analyzed by RP-HPLC. In vivo tolerability and pharmacokinetics were evaluated in albino rabbits. Rabbits were given an intravitreal injection of a PRINT microparticle suspension and levels of dexamethasone in vitreous humor, aqueous humor, and retina were determined at day 28, 56, and 84 by ELISA. Tolerability was assessed by ocular exams including slit lamp biomicroscopy and indirect ophthalmoscopy.

Results : SEM analysis showed uniform, controlled shape and size microparticles. Tunable and sustained release of dexamethasone from PRINT microparticle suspensions was demonstrated in vitro lasting >120 days. In an in vivo rabbit model, the microparticles were well tolerated and showed therapeutically relevant levels of dexamethasone (>0.1ug/mL) present in the retina and vitreous humor out to 84 days (Figure 1).

Conclusions : We demonstrate the ability to fabricate microparticles of uniform and reproducible size and shape for sustained release of dexamethasone over several months in vitro and in vivo using PRINT technology. PRINT microparticles allow for better reproducibility of release rates and the ability to deliver milligram quantities of steroids to the vitreous using small needle gauge sizes, reducing the frequency of intravitreal injections.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Figure 1: Dexamethasone concentration in albino rabbit ocular matrices.