LAUSR

Subcutaneous administration is a desired route for monoclonal antibodies (mAbs). However, formulating mAbs for small injection volumes at high concentrations with suitable stability and injectability is a significant challenge. Here we present a platform technology that combines the stability of crystalline antibodies with injectability and tunability of soft hydrogel particles. Composite alginate hydrogel particles were generated via a gentle centrifugal encapsulation process which avoids use of chemical reactions or an external organic phase. Crystalline suspension of anti-PD-1 antibody (pembrolizumab) was utilized as a model therapeutic antibody. Crystalline forms of the mAb encapsuled in the hydrogel particles led to stable, high concentration and injectable formulations. Formulation concentrations as high as 315 mg/ml antibody were achieved with encapsulation efficiencies in the range of 89-97%, with no perceivable increase in the number of antibody aggregates. Bioanalytical studies confirmed superior maintained quality of the antibody in comparison with formulation approaches involving organic phases and chemical reactions. We illustrated tuning the alginate particles' disintegration by utilizing partially oxide alginates. Crystalline mAb-laden particles were evaluated for their biocompatibility using cell-based in vitro assays. Furthermore, the pharmacokinetics of the subcutaneously delivered human ant-PD-1 mAb in crystalline antibody-laden alginate hydrogel particles in Wistar rats was evaluated. This article is protected by copyright. All rights reserved.