Effect of PEG molecular weight and PEGylation degree on the physical stability of PEGylated lysozyme

Morgenstern, Josefine; Baumann, Pascal; Brunner, Carina; Hubbuch, Jürgen

doi:10.1016/j.ijpharm.2017.01.040

Cited by 60 publications

(70 citation statements)

References 40 publications

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“…As a result, these interactions decrease the ΔH m values of BP/Q composites. Moreover, there is another interesting effect due to heating, which is known as the steric effect, and which appears within the molecules due to the arrangements of atoms . The steric effect can change the shapes of molecules and their bonds.…”

Section: Resultsmentioning

confidence: 99%

Thermal and dynamic mechanical properties of polyethylene glycol/quartz composites for phase change materials

Fauziyah

Hilmi

Zainuri

et al. 2019

J of Applied Polymer Sci

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Polyethylene glycol (PEG)/quartz (denoted as BP/Q) composites have been investigated as candidates of phase change materials (PCMs) due to their thermomechanical properties around the glass transition temperature as well as thermal properties between 30 and 600 C. Quartz (q-SiO 2 ) powders were extracted from local sand in Tanah Laut, Pelaihari, South Kalimantan, Indonesia. The composites were prepared by dispersing q-SiO 2 powders in the PEG matrix followed by the wet mixing process. The thermal properties of the composites were characterized using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), while the thermomechanical properties were examined using a dynamic mechanical analyzer (DMA) in a three-point bending mode around the PEG glass transition temperature range (−100-50 C). The morphology and interface bonding were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). From the DSC measurement, the endothermic peak of the composites showed a shift of approximately 7-12 C toward higher temperatures than that of the pure polymer. The melting enthalpy values (ΔH m ) of the BP/Q composites covered the required PCM application range, that is, between 139 and 182 J/g. The TGA of the composites showed that thermal degradation occurs in the range of 250-450 C. We found that solid-solid PCMs (ssPCMs) were successfully fabricated with the addition of 10 and 20 wt% q-SiO 2 . From DMA characterization, the BP/Q 20 wt% composite exhibited the maximum E' and the minimum energy dissipation (E"). Its E' value was approximately 250 MPa more than that of the pure PEG. The glass transition (T g ) temperatures of PEG and BP/Q composites (5, 10, and 20 wt%) were around −24.5, −19.1, −17.1, and − 5.3 C, respectively. In addition, the E" and tan δ values decreased with q-SiO 2 filler content. Furthermore, the Cole-Cole plots of the BP/Q composites revealed a better interfacial bonding between the q-SiO 2 and the PEG matrix in the composites with higher silica content. A compact morphology was shown by the BP/Q 20 wt% composite due to high silica concentration.

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Section: Resultsmentioning

confidence: 99%

Thermal and dynamic mechanical properties of polyethylene glycol/quartz composites for phase change materials

Fauziyah

Hilmi

Zainuri

et al. 2019

J of Applied Polymer Sci

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“…These surface modifications substantially increased the half‐life of liposomes and enabled the use of these drug delivery systems for new applications since long‐circulating liposomes could profit from the EPR and accumulate in tumors or sites of inflammation . In particular, PEG has already received much attention for its beneficial effects combined with drugs or nanocarrier systems, such as increasing stability and solubility, or decreasing toxicity and antigenicity . As PEG is a synthetic polymer, the molecular weight and its structure can be modified to fit individual needs.…”

Section: Long‐term Fate Of Clinically Relevant (Bioinspired) Nanomatementioning

confidence: 99%

Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials

et al. 2018

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Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed.

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“…As early as in 1977, the group of Abuchowski and Davis found an increased blood circulation half‐life and a reduced immunogenicity of PEGylated proteins compared to the native form . Additional positive effects of PEGylation are an increased thermal stability as well as a higher solubility allowing for higher concentrated protein formulations . Two successfully approved PEGylated protein drugs are interferon α‐2a (Pegasys, Hoffman‐LaRoche) for the treatment of hepatitis C and granulocyte‐colony stimulating factor (Neulasta, Amgen) for the treatment of leukemia.…”

Section: Introductionmentioning

confidence: 99%

Model‐Based Investigation on the Mass Transfer and Adsorption Mechanisms of Mono‐Pegylated Lysozyme in Ion‐Exchange Chromatography

Morgenstern

Wang

Baumann

et al. 2017

Biotechnology Journal

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Recent studies highlighted the potential of PEGylated proteins to improve stabilities and pharmacokinetics of protein drugs. Ion-exchange chromatography (IEX) is among the most frequently used purification methods for PEGylated proteins. However, the underlying physical mechanisms allowing for a separation of different PEGamers (proteins with a varying number of attached PEG molecules) are not yet fully understood. In this work, mechanistic chromatography modeling is applied to gain a deeper understanding of the mass transfer and adsorption/desorption mechanisms of mono-PEGylated proteins in IEX. Using a combination of the general rate model (GRM) and the steric mass action (SMA) isotherm, simulation results in good agreement with the experimental data are achieved. During linear gradient elution of proteins attached with PEG of different molecular weight, similar peak heights, and peak shapes at constant gradient length are observed. A superimposed effect of increased desorption rate and reduced diffusion rate as a function of the hydrodynamic radius of PEGylated proteins is identified to be the reason of this anomaly. That is why the concept of the diffusion-desorption-compensation effect is proposed. In addition to the altered elution orders, PEGylation results in a considerable decrease of maximum binding capacity. By using the SMA model in a kinetic formulation, the adsorption behavior of PEGylated proteins in the highly concentrated state is described mechanistically. An exponential increase in the steric hindrance effect with increasing PEG molecular weight is observed. This suggests the formation of multiple PEG layers in the interstitial space between bound proteins and an associated shielding of ligands on the adsorber surface to be the cause of the reduced maximum binding capacity. The presented in silico approach thus complements the hitherto proposed theories on the binding mechanisms of PEGylated proteins in IEX.

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Effect of PEG molecular weight and PEGylation degree on the physical stability of PEGylated lysozyme

Cited by 60 publications

References 40 publications

Thermal and dynamic mechanical properties of polyethylene glycol/quartz composites for phase change materials

Thermal and dynamic mechanical properties of polyethylene glycol/quartz composites for phase change materials

Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials

Model‐Based Investigation on the Mass Transfer and Adsorption Mechanisms of Mono‐Pegylated Lysozyme in Ion‐Exchange Chromatography

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