Fletcher Nathan A, Krebs Melissa D
Department of Chemical and Biological Engineering, Colorado School of Mines 1613 Illinois Street Golden CO 80401 USA
RSC Adv. 2018 Feb 28;8(16):8999-9005. doi: 10.1039/c7ra13014g. eCollection 2018 Feb 23.
Therapeutic antibodies are attractive treatment options for numerous diseases based on their ability to target and bind to specific proteins or antigens. Bevacizumab, an antiangiogenic antibody, has shown promise for multiple diseases, including various cancers and macular degeneration, where excessive VEGF secretion induces aberrant angiogenesis. In many cases local, sustained delivery of a therapeutic antibody would be preferable to maximize the therapeutic at the disease site, eliminate the need for repeated doses, and reduce systemic side effects. The biodegradable polysaccharides alginate and chitosan can electrostatically interact to form a polyelectrolyte complex (PEC), and have proved effective as a carrier for controlled release of antibodies. In this work, an alginate-chitosan PEC system was designed to produce targeted 30-day delivery of non-specific IgG and anti-VEGF antibodies. The release of anti-VEGF was slow relative to IgG release, suggesting that release rate is antibody specific and is based on the interactions of the PEC with charges present on the antibody surface. The anti-VEGF released from the PEC was shown to successfully inhibit VEGF-induced proliferation and angiogenesis throughout the 30-day test period.
治疗性抗体因其能够靶向并结合特定蛋白质或抗原,成为众多疾病颇具吸引力的治疗选择。贝伐单抗是一种抗血管生成抗体,已在多种疾病中展现出前景,包括各种癌症和黄斑变性,这些疾病中过量的血管内皮生长因子(VEGF)分泌会诱导异常血管生成。在许多情况下,局部、持续递送治疗性抗体将更可取,以在疾病部位最大化治疗效果,消除重复给药的需求,并减少全身副作用。可生物降解的多糖藻酸盐和壳聚糖可通过静电相互作用形成聚电解质复合物(PEC),并已被证明是一种有效的抗体控释载体。在这项工作中,设计了一种藻酸盐-壳聚糖PEC系统,以实现非特异性IgG和抗VEGF抗体的靶向30天递送。相对于IgG释放,抗VEGF的释放较慢,这表明释放速率具有抗体特异性,且基于PEC与抗体表面电荷的相互作用。在整个30天的测试期内,从PEC释放的抗VEGF被证明能够成功抑制VEGF诱导的增殖和血管生成。