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Preventing Physical Degradation of LABL-Fc-MOG BPI with Formulation Development Approaches
Xin, Lun
Xin, Lun
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Abstract
LABL-Fc-MOGR5 is a bifunctional peptide inhibitor (BPI) developed to modulate immune responses in multiple sclerosis (MS), especially primary progressive MS (PPMS). Despite its therapeutic potential, LABL-Fc-MOGR5 suffers from poor physical stability, precipitating rapidly under standard formulation conditions. This study employed a high-throughput, multi-phase formulation development strategy to enhance its conformational and colloidal stability. In Phase 1, intrinsic fluorescence differential scanning fluorometry (IF-DSF) and PEG solubility assays evaluated 96 formulations across varied pH, buffer types, and excipients. The results highlighted pH sensitivity and ionic strength effects, with divalent buffers (e.g., citrate, succinate) and excipients such as sucrose and hydroxypropyl-beta-cyclodextrin (HP-βCD) contributing to improved stability. Phase 2 involved a definitive screening design (DSD) to optimize formulation factors including buffer type, excipients, and surfactant level. The final optimized formulation at pH 5.3 contains 10 mM sodium acetate, pH 5.3, 125 mM sucrose, 150 mM HBP-LB-BCD, and 0.025% PS80. This formulation significantly outperformed the initial formulation to reduce aggregation, fragmentation, and particle formation under stress. This study underscores the importance of excipient selection in stabilizing therapeutic fusion proteins and provides a robust formulation pathway for advancing LABL-Fc-MOGR5 to clinical evaluation.
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Date
2025-08-31
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University of Kansas
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This item contains archived web content.
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Xin_ku_0099M_20171.pdf
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- Embargoed until 2026-08-31
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Keywords
Pharmaceutical sciences, Chemistry, Biophysics, Bispecific Peptide Inhibitors, Design of Experiment, Formulation Screening, HP-Betacyclodextrin, Physical Degradation