Stability, Formulation, and Delivery of Biopharmaceuticals

Mahler, Hanns‐Christian; Allmendinger, Andrea

doi:10.1002/9783527699124.ch14

Cited by 7 publications

(2 citation statements)

References 57 publications

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“…The governing equation for steady state flow through a pipe (eq ) is derived using this constitutive relationship to model the injection pressure ( P ) as a function of flow rate ( Q ), radius ( R ), length ( l ), and viscosity. − This model has been used by Paxton et al to predict the bioprinting window for a variety of 3D printing materials . Almendinger et al validated the model for shear-thinning antibody solutions and used it to predict the extrusion pressure in a variety of injection scenarios. ,− Our group validated the model for physically cross-linked hydrogels, demonstrating its applicability for two physical hydrogels with distinct cross-linking mechanisms (polymer–nanoparticle interactions and ionic cross-linking) …”

Section: Mechanical Consideration For Designing Injectable Hydrogelsmentioning

confidence: 99%

Translational Applications of Hydrogels

et al. 2021

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Advances in hydrogel technology have unlocked unique and valuable capabilities that are being applied to a diverse set of translational applications. Hydrogels perform functions relevant to a range of biomedical purposesthey can deliver drugs or cells, regenerate hard and soft tissues, adhere to wet tissues, prevent bleeding, provide contrast during imaging, protect tissues or organs during radiotherapy, and improve the biocompatibility of medical implants. These capabilities make hydrogels useful for many distinct and pressing diseases and medical conditions and even for less conventional areas such as environmental engineering. In this review, we cover the major capabilities of hydrogels, with a focus on the novel benefits of injectable hydrogels, and how they relate to translational applications in medicine and the environment. We pay close attention to how the development of contemporary hydrogels requires extensive interdisciplinary collaboration to accomplish highly specific and complex biological tasks that range from cancer immunotherapy to tissue engineering to vaccination. We complement our discussion of preclinical and clinical development of hydrogels with mechanical design considerations needed for scaling injectable hydrogel technologies for clinical application. We anticipate that readers will gain a more complete picture of the expansive possibilities for hydrogels to make practical and impactful differences across numerous fields and biomedical applications.

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Section: Mechanical Consideration For Designing Injectable Hydrogelsmentioning

confidence: 99%

Translational Applications of Hydrogels

et al. 2021

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“…However, they pose unique challenges due to their low stability as compared with small-molecule drugs. Unfolding and aggregate formation can occur in almost every biopharmaceutical process, ranging from production, purification, formulation, storage, transportation, delivery, to clinical administration with current systems formulated as a liquid solution or suspension, or lyophilized product . Therefore, it is critical to consider factors that influence protein structure and stability at every stage of biopharmaceutical development and production.…”

Section: Introductionmentioning

confidence: 99%

Impact of Confinement within a Hydrogel Mesh on Protein Thermodynamic Stability and Aggregation Kinetics

Ghassemi,

Leach

2024

Mol. Pharmaceutics

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Though protein stability and aggregation have been well characterized in dilute solutions, the influence of a confining environment that exists (e.g., in intercellular and tissue spaces and therapeutic formulations) on the protein structure is largely unknown. Herein, the effects of confinement on stability and aggregation were explored for proteins of different sizes, stability, and hydrophobicity when encapsulated in hydrophilic poly(ethylene glycol) hydrogels. Denaturation curves show linear correlations between confinement size (mesh size) and thermodynamic stability, i.e., unfolding free energy and surface area accessible for solvation (represented by m-value). Two clusters of protein types are identifiable from these correlations; the clusters are defined by differences in protein stability, surface area, and aggregation propensity. Proteins with higher stability, larger surface area, and lower aggregation propensity (e.g., lysozyme and myoglobin) are less affected by the confinement imposed by mesh size than proteins with lower stability, smaller surface area, and higher aggregation propensity (e.g., growth hormone and aldehyde dehydrogenase). According to aggregation kinetics measured by thioflavin T fluorescence, confinement in smaller mesh sizes resulted in slower aggregation rates than that in larger mesh sizes. Compared to that in buffer solution, the confinement of a hydrophobic protein (e.g., human insulin) in the hydrogels accelerates protein aggregation. Conversely, the confinement of a hydrophilic protein (e.g., human amylin) in the hydrogels decelerates or prevents aggregation, with the rates of aggregation inversely proportional to mesh size. These findings provide new insights into protein conformational stability in confined microenvironments relevant to various cellular, tissue, and therapeutics scenarios.

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Advances in Freeze Drying of Biologics and Future Challenges and Opportunities

Bhatnagar

Tchessalov

2020

Drying Technologies for Biotechnology and Pharmaceutical Applications

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Stability, Formulation, and Delivery of Biopharmaceuticals

Cited by 7 publications

References 57 publications

Translational Applications of Hydrogels

Translational Applications of Hydrogels

Impact of Confinement within a Hydrogel Mesh on Protein Thermodynamic Stability and Aggregation Kinetics

Advances in Freeze Drying of Biologics and Future Challenges and Opportunities

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