Crystalline Antibody‐Laden Alginate Particles: A Platform for Enabling High Concentration Subcutaneous Delivery of Antibodies
Name
Adv Healthcare Materials - 2023 - Erfani - Crystalline Antibody‐Laden Alginate Particles A Platform for Enabling High.pdf
Description
Published version
Size
5.07 MB
Format
Adobe PDF
Checksum (MD5)
39e510acf9831b61a2b1a7bd1724f89a
Author(s)
Erfani, Amir
Schieferstein, Jeremy M
Reichert, Paul
Narasimhan, Chakravarthy N
Pastuskovas, Cinthia
Parab, Vaishali
Simmons, Denarra
Yang, Xiaoyu
Shanker, Apoorv
Hammond, Paula
Date Issued
June 2023
Journal
Advanced Healthcare Materials
Publisher
Wiley
Citation
Erfani, Amir, Schieferstein, Jeremy M, Reichert, Paul, Narasimhan, Chakravarthy N, Pastuskovas, Cinthia et al. 2023. "Crystalline Antibody‐Laden Alginate Particles: A Platform for Enabling High Concentration Subcutaneous Delivery of Antibodies." Advanced Healthcare Materials, 12 (15).
Version
Final published version
Abstract
Subcutaneous (SC) 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, this work presents a platform technology that combines the stability of crystalline antibodies with injectability and tunability of soft hydrogel particles. Composite alginate hydrogel particles are generated via a gentle centrifugal encapsulation process which avoids use of chemical reactions or an external organic phase. Crystalline suspension of anti‐programmed cell death protein 1 (PD‐1) antibody (pembrolizumab) is utilized as a model therapeutic antibody. Crystalline forms of the mAb encapsuled in the hydrogel particles lead to stable, high concentration, and injectable formulations. Formulation concentrations as high as 315 mg mL−1 antibody are achieved with encapsulation efficiencies in the range of 89–97%, with no perceivable increase in the number of antibody aggregates. Bioanalytical studies confirm superior maintained quality of the antibody in comparison with formulation approaches involving organic phases and chemical reactions. This work illustrates tuning the alginate particles’ disintegration by using partially oxide alginates. Crystalline mAb‐laden particles are evaluated for their biocompatibility using cell‐based in vitro assays. Furthermore, the pharmacokinetics (PK) of the subcutaneously delivered human anti‐PD‐1 mAb in crystalline antibody‐laden alginate hydrogel particles in Wistar rats is evaluated.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial
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DOI of Published Version
https://doi.org/10.1002/adhm.202202370
