Adsorption of Monoclonal Antibodies to Glass Microparticles

Hoehne, Matthew; Samuel, Fauna; Dong, Aichun; Wurth, Christine; Mahler, Hanns‐Christian; Carpenter, John F.; Randolph, Theodore W.

doi:10.1002/jps.22275

Cited by 50 publications

(47 citation statements)

References 33 publications

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“…[34] The amount of KGF-2 on the surface was then estimated by multiplying the specific surface area by an estimated surface coverage of 2 mg/m 2 (Table 3). Estimated maximum ice-water surface coverage for interferon- γ, a similarly-sized protein, were reported as 4.5 mg/m 2 , and protein adsorption to a variety of surfaces such as glass[35, 36], silica[35, 36], polystyrene[37] and cellulose[36] has been reported to range from 2–4 mg/m 2 ; thus our estimate of 2mg/m 2 may yield a conservative estimate of the amount of KGF-2 on the surface of lyophilized samples.…”

Section: Discussionmentioning

confidence: 99%

Storage stability of keratinocyte growth factor-2 in lyophilized formulations: Effects of formulation physical properties and protein fraction at the solid–air interface

Devineni

Gonschorek

Cicerone

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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Lyophilized formulations of keratinocyte growth factor-2 (KGF-2) were prepared with a range of disaccharide (sucrose or trehalose) and hydroxyethyl starch (HES) mass ratios. Protein degradation was assessed as a function of time of storage of the dried formulations at 40, 50 and 60 °C. Lyophilized and stored samples were rehydrated, and protein degradation was quantified by measuring loss of monomeric protein with size exclusion chromatography and by determining chemical degradation in the soluble fraction with reverse-phase chromatography. The secondary structure of the protein in the lyophilized formulations was studied with infrared spectroscopy. The magnitudes of degradation were compared the key physical properties of the formulations including retention of protein native secondary structure, glass transition temperature (Tg), inverse mean square displacements −1 for hydrogen atoms (fast β relaxation), and the relaxation time τβ, which correlates with relaxation due to fast Johari-Goldstein motions in the glass[1]. In addition, specific surface areas of the lyophilized formulations were determined by Brunauer-Emmet-Teller analysis of krypton adsorption isotherms and used to estimate the fraction of the KGF-2 molecules residing at the solid-air interface. KGF-2 degradation rates were highest in formulations wherein the protein’s structure was most perturbed, and wherein β relaxations were fastest, but the dominant factor governing KGF-2 degradation in freeze-dried formulations was the fraction of the protein found at the glass solid-air interface.

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Section: Discussionmentioning

confidence: 99%

Storage stability of keratinocyte growth factor-2 in lyophilized formulations: Effects of formulation physical properties and protein fraction at the solid–air interface

Devineni

Gonschorek

Cicerone

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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“…For this case, front face measurements with cuvettes rotated to a measurement angle of ideally 34° or 56° are the better option 153. These setups have also been used to measure protein adsorbed to beads154,155 and are in principle also possible for protein particles even though applications for protein particles are still lacking. Although the protein concentration should be adjusted to show an absorbance at the excitation wavelength not higher than 0.1 in normal fluorescence measurements because of the inner filter effect, this is less critical for front face measurements.…”

Section: Spectroscopic Methodsmentioning

confidence: 99%

Particles in Therapeutic Protein Formulations, Part 1: Overview of Analytical Methods

Zölls¹,

Tantipolphan²,

Wiggenhorn³

et al. 2012

Journal of Pharmaceutical Sciences

203

159

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“…Aggregates can become visible to the naked eye if they are sufficiently large and/or undergo phase separation [87–89]. If unfolding / aggregation is mediated by protein adsorption to bulk interfaces [90–92], and/or chemical changes such as deamidation [93–95], oxidation and other reactions [96,97], or fragmentation [98,99], then additional steps may also be kinetically important in the possible aggregation mechanism(s).…”

Section: Figurementioning

confidence: 99%

Therapeutic protein aggregation: mechanisms, design, and control

Roberts

2014

Trends in Biotechnology

367

309

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While it is well known that proteins are only marginally stable in their folded states, it is often less well appreciated that most proteins are inherently aggregation-prone in their unfolded or partially unfolded states, and the resulting aggregates can be extremely stable and long-lived. For therapeutic proteins, aggregates are a significant risk factor for deleterious immune responses in patients, and can form via a variety of mechanisms. Controlling aggregation using a mechanistic approach may allow improved design of therapeutic protein stability, as a complement to existing design strategies that target desired protein structures and function. Recent results highlight the importance of balancing protein environment with the inherent aggregation propensities of polypeptide chains.

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Adsorption of Monoclonal Antibodies to Glass Microparticles

Cited by 50 publications

References 33 publications

Storage stability of keratinocyte growth factor-2 in lyophilized formulations: Effects of formulation physical properties and protein fraction at the solid–air interface

Storage stability of keratinocyte growth factor-2 in lyophilized formulations: Effects of formulation physical properties and protein fraction at the solid–air interface

Particles in Therapeutic Protein Formulations, Part 1: Overview of Analytical Methods

Therapeutic protein aggregation: mechanisms, design, and control

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