Center for Molecular and Engineering Thermodynamics, Department of Chemical and Biomolecular Engineering, University of Delaware , Newark, Delaware 19716, United States.
Mol Pharm. 2013 Oct 7;10(10):3582-91. doi: 10.1021/mp400006g. Epub 2013 Sep 6.
Subcutaneous antibody dosing formulations comprising solid suspensions have the potential to reduce dosage viscosity and injection volume. Gel beads of three therapeutic antibodies were prepared to determine the feasibility of such formulations. The beads were formed directly from aqueous solution within 0.1-4 days upon addition of biocompatible precipitating agents under conditions compatible with the use of stabilizing excipients. The phase behavior of antibody gel beads and their mechanical characteristics were measured. Gel beads were characterized by reduced elastic moduli of 0.4-1.0 MPa, as measured by atomic force microscopy, and completely redissolved within 10-20 min under physiologic conditions, in vitro. Crystalline particles could also be prepared in some cases and were found to have reduced elastic moduli 3 orders of magnitude greater than those for the gel beads. Both crystalline and gel particles had protein concentrations of 100-180 mg/mL within the dense phase. Protein stored within the dense phase was recoverable after 40 days of incubation at room temperature or 4 °C.
包含固体混悬剂的皮下抗体给药制剂有可能降低剂量粘度和注射体积。制备了三种治疗性抗体的凝胶珠，以确定此类制剂的可行性。在添加生物相容性沉淀剂后，在与使用稳定剂赋形剂相容的条件下，这些凝胶珠在 0.1-4 天内直接从水溶液中形成。测量了抗体凝胶珠的相行为及其机械特性。通过原子力显微镜测量，凝胶珠的弹性模量降低到 0.4-1.0 MPa，并且在生理条件下在 10-20 分钟内完全重新溶解，体外。在某些情况下也可以制备结晶颗粒，并且发现它们的弹性模量比凝胶珠低 3 个数量级。结晶颗粒和凝胶颗粒在致密相中都具有 100-180 mg/mL 的蛋白质浓度。在室温或 4°C 下孵育 40 天后，可从致密相中回收储存的蛋白质。
