Iyer Shwetha, Lee Cameron, Amiji Mansoor M
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Northeastern University, Boston, MA, 02115, USA.
Novartis Biomedical Research, Cambridge, MA, 02139, USA.
Drug Deliv Transl Res. 2025 Jan 24. doi: 10.1007/s13346-025-01795-y.
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.
年龄相关性黄斑变性（AMD）是老年人群中心视力丧失的主要原因之一。贝伐单抗是一种全长人源化单克隆抗VEGF抗体，是常用于治疗AMD的非标签药物。然而，贝伐单抗和其他抗VEGF抗体的给药方案需要每月进行玻璃体内注射，随后每隔4 - 16周定期进行玻璃体内注射。2021年，美国食品药品监督管理局（FDA）批准了一种创新的雷珠单抗（Susvimo）端口递送系统，该系统可植入玻璃体内以缓慢释放活性成分抗VEGF抗体，并将注射频率降低至每6个月一次。一种利用包裹全长抗体（如贝伐单抗）的聚合物缓释微球的方法对患者会更加友好，因为它可以通过玻璃体内注射，避免手术植入。虽然微球包封传统上对小分子疏水药物是成功的，但我们评估了两种不同的聚合物，即聚（D，L - 丙交酯 - 乙交酯）（PLGA）和聚己内酯（PCL），并发现利用像PCL这样缓慢降解的疏水聚合物用于大型蛋白质治疗的益处。使用PCL聚合物的传统双乳液制备方法，我们可以生产出包裹贝伐单抗抗体的微球，并证明生物活性治疗剂的释放长达60天。这种新方法可能会在我们这个领域带来重大进展，并有可能为未来的研究开辟新途径。
