Abstract
Purpose :
Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs are used to treat age-related macular degeneration (AMD), but repeated IVT injections are associated with potential adverse effects and represent a major workload for ophthalmology clinics. Thus, the need for less frequent dosing of therapeutic anti-VEGF drugs persists. Bevacizumab (BV) is an anti-VEGF antibody used off label to treat AMD. The purpose of this study was to investigate, using BV as a model, if a biological anti-VEGF drug could be encapsulated within a sol-gel derived biodegradable silica matrix and remain active after a controlled release facilitated by the erosion of the matrix.
Methods :
BV was encapsulated in a silica matrix using sol-gel chemistry and spray-drying. The silica matrix dissolution, BV release rate and BV activity of different silica microparticle-silica hydrogel composite formulations were studied in vitro. The dissolution studies were carried out in sink conditions (accelerated dissolution test) and the cumulative release and the total content of BV in the formulations were analyzed by HPLC. The dissolution of the silica matrix was quantified colorimetrically. The VEGF binding activity of the released BV was studied in ELISA and the capability of BV to inhibit VEGF induced cell proliferation was tested.
Results :
The silica-silica composite formulations contained 20-40 mg of BV per 1 ml of the formulation. The burst release of BV in all ten formulations was below 9 wt% (of total BV content) and a sustained release of BV, strictly controlled by the erosion of the silica matrix was demonstrated. The release rates of BV from the silica matrix varied from 2-16 days in accelerated dissolution test, depending on the BV load% and the molar ratio of water to silica alkoxide of the silica-BV sols. These would correspond to 2.5 to 13 months in vivo release in the vitreous, using appropriate in vitro-in vivo correlation factor for the accelerated dissolution test. Furthermore, the released BV was shown to retain its binding activity and capability to inhibit the function of VEGF.
Conclusions :
Efficient encapsulation and varying in vitro release rates of active BV were achieved in the studies. These findings support the hypothesis that anti-VEGF drugs can be encapsulated within a biodegradable silica matrix to facilitate a controlled and sustained release.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.