Abstract
Purpose :
Even though anti-vascular endothelial growth factor (VEGF) therapy is successful for a majority of patients, there is a growing number of subset of patients that does not respond to monthly monotherapy but respond to a combination therapy such as corticosteroids and anti-VEGF. The purpose of this study was to characterize the extended and controlled dual release of dexamethasone (DEX) and aflibercept (AFL) from a single drug delivery system (DDS).
Methods :
Two different preparations of single-emulsion poly(lactic-co-glycolic acid) (PLGA) nanoparticles were made by varying vortex and sonication time, resulting in DEX-A and DEX-B. Size distribution and mean diameter were analyzed using Nanoparticle Tracking Analysis. The aflibercept was encapsulated into PLGA microspheres using double emulsion technique. The DDS for single release consisted of 20 mg of DEX nanoparticles (DEX-np) suspended within a biodegradable N-isopropylacrylamide/poly(ethylene glycol)-co-(L-lactic acid) diacrylate/ (NIPAAm/PEG-PLLA-DA) thermoresponsive hydrogel. The dual release consisted of 20 mg of DEX-np and 20 mg of AFL microspheres (AFL-ms) suspended within the hydrogel. DEX release in vitro, with and without AFL-ms, was quantified using NanoDrop™ OneC. Iodine-125 radiolabeled AFL was used to measure encapsulation efficiency into the hydrogel and in vitro release. The initial burst was calculated by quantifying total drug release in the first 24 hours.
Results :
Average diameter was 138.9±6.2 and 267±55 nm for DEX-A and DEX-B, respectively. The single release of DEX-A and DEX-B had an initial burst of 288 and 301.2 ug, respectively. The addition of AFL-ms did not significantly alter the interval or steady state release of dexamethasone for the first 60 days for DEX-A nor DEX-B. Conversely, increased release rates were seen for AFL in the presence of DEX-np in the first 14 days. The addition of DEX-np reduced the encapsulation efficiency of AFL-ms into the hydrogel by 16.3%, the initial burst by 1.3% and the final drug load dose by 7.9%.
Conclusions :
DEX release kinetics from a hydrogel DDS were not significantly affected by the presence of ALF-ms. AFL release rates from a hydrogel DDS increased in the presence of DEX-np. This study suggests that an extended and controlled release of both DEX and AFL from a single DDS can be achieved.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.