ACS Applied Materials & Interfaces · 2022 · 19 citations · 39 references
PharmacyPharmaceuticsPharmacokineticsDrug DeliveryPharmaceutical FormulationPolymer ChemistryDiabetes ManagementDiabetes MellitusDiabetes Mellitus BiochemistryInsulin TherapyPolymeric Drug Delivery SystemsProtein DeliveryHuman InsulinInsulin Administration SafetyInsulin BiochemistryInsulin Injection SafetyInsulin PhysiologyInsulin StabilityInsulin StorageParenteral Drug Administration
Cu-labeled pTrMA showed excretion of 78-79% ID/cc within 24 h and minimal liver accumulation at 6-8% ID/cc when studied out to 120 h. Further, the plasma lifetime of insulin in mice was not altered by added pTrMA. Formulating insulin with 2 mol equiv of pTrMA improved the stability of insulin to standard storage conditions: 46 weeks at 4 °C yielded 87.0% intact insulin with pTrMA present as compared to 7.8% intact insulin without the polymer. The mechanism by which pTrMA-stabilized insulin was revealed to be a combination of inhibiting deamidation of amino acid residues and preventing fibrillation, followed by aggregation of inactive and immunogenic amyloids all without complexing insulin into its hexameric state, which could delay the onset of insulin activity. Based on the data reported here, we suggest that pTrMA stabilizes insulin as an excipient without adverse effects in vivo and is promising to investigate further for the safe formulation of insulin.
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Supramolecular PEGylation of biopharmaceuticals
Matthew J. Webber, Eric A. Appel, Brittany Vinciguerra et al. · Proceedings of the National Academy of Sciences · 2016 · 207 citations · Full text