Abstract
Purpose :
Current treatment options for back-of-the-eye diseases such as age-related macular degeneration (AMD) are limited to invasive and painful intra-vitreal injections of anti-angiogenic antibodies that also carry the risks of endophthalmitis (infections), intraocular inflammation and retinal detachment. This study tested the hypothesis that drug carriers injected into the subconjunctival space can act as suitable depots for sustained ocular delivery of anti-VEGF antibodies to the posterior eye segment.
Methods :
Nanoliposomes were fabricated using conventional methods, tagged with fluorescent dye. Using our own model of ex vivo scleral penetration, we studied the accumulation of liposomes in explanted porcine sclera, by fluorescence imaging. Neutral and charged liposomes were compared with PLGA microparticles fabricated using solid/oil/water emulsion technique, and tagged with a red dye. Lucentis® (anti-VEGF) was loaded into PLGA carriers using the solid/oil/water emulsion method, which was followed by studies on in vitro drug release.
Results :
Using the solid/oil/water emulsion fabrication method, the anti-VEGF molecule, Lucentis®, was successfully entrapped in micron-sized PLGA carriers. Subsequent in vitro release studies revealed that the release of bioactive Lucentis® was sustained over period of up to 15 days. Liposomes in the size range of 90 – 110 nm, on the other hand, exhibited varying degrees of anti-VEGF encapsulation. The distribution and transcleral transport of the liposomes in the mouse eye after subconjunctival injection was found to be dependent on surface charge and size.
Conclusions :
Subconjunctival administration of both microsized and nanosized particles has the potential to act as drug depots for ocular delivery of anti-VEGF antibodies. The micron-sized PLGA carriers cannot readily diffuse into the intra-scleral spaces but can function as drug-releasing depots within the subconjunctival space. Nanosized liposomes can either function as subconjunctival depots or as intrascleral depots (if they diffuse into the sclera). The potential of using these modes of ocular delivery will have to be confirmed by efficacy studies in animal models of the disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.