Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot.

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics. Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease.

维持具有治疗相关性水平的广谱中和抗体（bnAbs）对于实现针对传染病的被动免疫是必要的。 不幸的是，保护作用仅在这些广谱中和抗体在体内保持足够高浓度时才持续存在。 不良的药代动力学和繁琐的给药方式是需要解决的两个挑战，以便使使用广谱中和抗体进行暴露前和暴露后预防变得可行和有效。 在这项工作中，我们开发了一种超分子水凝胶作为一种可注射的皮下储库，用于封装和递送抗体药物。 这种聚合物 - 纳米颗粒（PNP）水凝胶具有可注射药物递送载体所需的剪切变稀和自愈合特性。 体外药物释放试验和扩散测量表明，PNP水凝胶可防止突释并减缓封装抗体的释放。 在临床前小鼠模型中，将从PNP水凝胶递送针对SARS - CoV - 2的广谱中和抗体与标准给药途径进行了比较。 我们开发了一个多室模型来了解这些皮下储库材料调节释放抗体药代动力学的能力；该模型被外推以探索新型材料成功递送具有不同药代动力学特征的相关抗体治疗药物所需的条件。 维持具有治疗相关性水平的广谱中和抗体（bnAbs）对于实现针对传染病的被动免疫是必要的。