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dc.contributor.authorErfani, Amir
dc.contributor.authorSchieferstein, Jeremy M
dc.contributor.authorReichert, Paul
dc.contributor.authorNarasimhan, Chakravarthy N
dc.contributor.authorPastuskovas, Cinthia
dc.contributor.authorParab, Vaishali
dc.contributor.authorSimmons, Denarra
dc.contributor.authorYang, Xiaoyu
dc.contributor.authorShanker, Apoorv
dc.contributor.authorHammond, Paula
dc.contributor.authorDoyle, Patrick S
dc.date.accessioned2025-02-28T21:33:05Z
dc.date.available2025-02-28T21:33:05Z
dc.date.issued2023-06
dc.identifier.urihttps://hdl.handle.net/1721.1/158280
dc.description.abstractSubcutaneous (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<jats:sup>−1</jats:sup> 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.en_US
dc.language.isoen
dc.publisherWileyen_US
dc.relation.isversionof10.1002/adhm.202202370en_US
dc.rightsCreative Commons Attribution-Noncommercialen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en_US
dc.sourceWileyen_US
dc.titleCrystalline Antibody‐Laden Alginate Particles: A Platform for Enabling High Concentration Subcutaneous Delivery of Antibodiesen_US
dc.typeArticleen_US
dc.identifier.citationErfani, 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).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.relation.journalAdvanced Healthcare Materialsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2025-02-28T21:19:01Z
dspace.orderedauthorsErfani, A; Schieferstein, JM; Reichert, P; Narasimhan, CN; Pastuskovas, C; Parab, V; Simmons, D; Yang, X; Shanker, A; Hammond, P; Doyle, PSen_US
dspace.date.submission2025-02-28T21:19:08Z
mit.journal.volume12en_US
mit.journal.issue15en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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