Abstract
Age-related macular degeneration (AMD) is one of the leading causes of central vision loss in the elderly population. Bevacizumab, a full-length humanized monoclonal anti-VEGF antibody, is commonly used off-label drug to treat AMD. However, the dosing regimen of bevacizumab and other anti-VEGF antibodies requires monthly intravitreal injections followed by regular intravitreal injections at 4–16-week intervals. In 2021, the FDA approved an innovative port delivery system of ranibizumab (Susvimo ® ) that can be implanted intravitreally to slowly release the active ingredient anti-VEGF antibody and reduce injection frequency to once every 6 months. An approach utilizing polymeric slow-release microspheres encapsulating a full-length antibody, such as bevacizumab, would be much more patient-friendly because it could be injected intravitreally, avoiding surgical implantation. While microsphere encapsulation is traditionally successful for small molecule hydrophobic drugs, we assessed two different polymers, namely poly(D, L-lactide-co-glycolide) (PLGA) and poly(epsilon-caprolactone) (PCL) and discovered the benefits of utilizing a slow degrading hydrophobic polymer such as PCL for large protein therapeutic. Using the traditional double emulsion fabrication method with PCL polymer, we could produce microspheres that encapsulate bevacizumab antibody and demonstrate the release of biologically active therapeutic agent for up to 60 days. This novel approach could lead to significant advancements in our field and potentially open new avenues for future research. Graphical Abstract