Purchase this article with an account.
KG Carrasquillo, J Ricker, IK Rigas, AP Adamis; Controlled Delivery of Anti-VEGF Aptamer EYE001 With Poly(lactic-co-glycolic)acid Microspheres . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2324.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To develop a controlled-drug delivery system for the long-term inhibition of vascular endothelial growth factor (VEGF) and its mediated responses. Method: Poly(lactic-co-glycolic)acid (PLGA) microspheres containing anti-VEGF RNA aptamer EYE001 formulations in the solid-state were developed by an oil-in-oil solvent evaporation process. In vitro experiments were performed to characterize the release profiles. Stability and bioactivity of the released drug were assayed by monitoring EYE001 ability to inhibit VEGF-induced cell proliferation in human umbilical vein endothelial cells (HUVECs). Cell proliferation experiments were conducted with aptamer aliquots collected after short-term, mid-term, and long-term release time points. In order to investigate the feasibility of this polymer device as a potential transcleral delivery device, an in-vitro apparatus was developed to assess polymer hydration and degradation through rabbit sclera and subsequent delivery through it. Results: PLGA microspheres were able to deliver EYE001 in a sustained manner, with an average rate of 2 µg/day over a period of 20 days. Solid-state stabilization of the aptamer with disaccharide trehalose prior to lyophilization and encapsulation in PLGA rendered the drug more stable after release. Cell proliferation experiments demonstrate that the bioactivity of the aptamer was preserved after release, as indicated by inhibition of endothelial cell proliferation after incubation with VEGF. Microspheres packed into a sealed chamber and placed onto the "orbital" part of a rabbit sclera for a period of six days became hydrated and started to degrade, as shown by scanning electron microscopy (SEM). As a result, the aptamer was delivered from the microspheres through the sclera, as determined spectrophotometrically. Conclusion: The feasibility of loading aptamer containing microspheres into a device and placing it on the orbital surface of the sclera was assessed and shown to be effective. RNA aptamer EYE001 encapsulated in PLGA was delivered over a period of 20 days with optimal activity. This method represents a promising approach for the transcleral delivery of drugs and the treatment of choroidal and retinal diseases.
This PDF is available to Subscribers Only