Change search
Link to record
Permanent link

Direct link
Publications (10 of 35) Show all publications
Martínez, C., Amery, L., De Paoli, G., Elofsson, U., Millqvist-Fureby, A., Kwok, S., . . . Paulsson, M. (2023). Examination of the Protein Drug Supply Chain in a Swedish University Hospital: Focus on Handling Risks and Mitigation Measures. Journal of Pharmaceutical Sciences
Open this publication in new window or tab >>Examination of the Protein Drug Supply Chain in a Swedish University Hospital: Focus on Handling Risks and Mitigation Measures
Show others...
2023 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017Article in journal (Refereed) Epub ahead of print
Abstract [en]

Protein drugs, such as monoclonal antibodies, have proved successful in treating cancer and immune system diseases. The structural complexity of these molecules requires careful handling to ensure integrity and stability of the drug. In this study, a failure mode and effects analysis was performed based on a Gemba Walk method in a Swedish University Hospital. The Gemba Walk is focused on pharmacists observing the actual supply process steps from distributor, pharmacy cleanroom to patient administration. Relevant protein drugs are chosen based on sales statistics within the hospital and the corresponding wards were observed. Further is the Double Diamond design method used to identify major risks and deliver mitigation strategies. The study identified potential stress factors such as temperature, shock by impact, shaking, vibration and light exposure. There were also risks associated with porters’ and healthcare professionals’ lack of awareness and access to information. These risk factors may cause loss of efficacy and quality of the protein drug, potentially leading to patient safety concerns. In this study, a simulation is also performed to list measures that theoretically should be in place to ensure the quality of the protein drug, for example validated and protocol-based compounding in cleanroom, training and validated transports. © 2023 The Authors

Place, publisher, year, edition, pages
Elsevier B.V., 2023
Keywords
Chemical stability, Immunotherapy, Injectables, Monoclonal antibodies, Protein aggregation, Stability, Transport
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:ri:diva-65624 (URN)10.1016/j.xphs.2023.05.003 (DOI)2-s2.0-85162256505 (Scopus ID)
Note

This work has received support from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking (RealHOPE grant n° 101007939 ).

Available from: 2023-06-29 Created: 2023-06-29 Last updated: 2023-12-07Bibliographically approved
Västberg, A., Bolinsson, H., Leeman, M., Nilsson, L., Nylander, T., Sejwal, K., . . . Elofsson, U. (2023). Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques. International Journal of Pharmaceutics, 637, Article ID 122829.
Open this publication in new window or tab >>Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques
Show others...
2023 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 637, article id 122829Article in journal (Refereed) Published
Abstract [en]

Three orthogonal techniques were used to provide new insights into thermally induced aggregation of the therapeutic protein Somatropin at pH 5.8 and 7.0. The techniques were Dynamic Light Scattering (DLS), Asymmetric Flow-Field Flow-Fractionation (AF4), and the TEM-based analysis system MiniTEM™. In addition, Differential Scanning Calorimetry (DSC) was used to study the thermal unfolding and stability. DSC and DLS were used to explain the initial aggregation process and aggregation rate at the two pH values. The results suggest that less electrostatic stabilization seems to be the main reason for the faster initial aggregation at pH 5.8, i.e., closer to the isoelectric point of Somatropin. AF4 and MiniTEM were used to investigate the aggregation pathway further. Combining the results allowed us to demonstrate Somatropin's thermal aggregation pathway at pH 7.0. The growth of the aggregates appears to follow two steps. Smaller elongated aggregates are formed in the first step, possibly initiated by partly unfolded species. In the second step, occurring during longer heating, the smaller aggregates assemble into larger aggregates with more complex structures. © 2023 The Author(s)

Place, publisher, year, edition, pages
Elsevier B.V., 2023
Keywords
human growth hormone, differential scanning calorimetry, photon correlation spectroscopy, Calorimetry, Differential Scanning, Dynamic Light Scattering
National Category
Physical Chemistry
Identifiers
urn:nbn:se:ri:diva-64673 (URN)10.1016/j.ijpharm.2023.122829 (DOI)2-s2.0-85151369842 (Scopus ID)
Note

Correspondence Address: Västberg, A.; Research Institutes of Sweden, Drottning Kristinas väg 61B, Sweden; email: amanda.vastberg@ri.se; Funding details: VINNOVA, 2018-04730; Funding text 1: The authors thank Malvern Analytical AB for the opportunity to use their automated PEAQ DSC and Zetasizer Ultra instruments, and especially thanks to Dr. Natalia Markova for valuable discussions on the DSC measurements and data, and Dr. Hanna Jankevics-Jones for valuable discussions on the DLS measurements and data. This research was funded by the Swedish Governmental Agency for Innovation Systems (VINNOVA) Research Council trough the competence center NextBioForm under grant number 2018-04730.; Funding text 2: This research was funded by the Swedish Governmental Agency for Innovation Systems (VINNOVA) Research Council trough the competence center NextBioForm under grant number 2018-04730.

Available from: 2023-05-15 Created: 2023-05-15 Last updated: 2023-12-07Bibliographically approved
Åkerlund, T., Zakikhany, K., Löfström, C., Lindmark, E., Källberg, H., Elofsson, U., . . . Björndal, Å. S. (2021). Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection. Medrxiv
Open this publication in new window or tab >>Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection
Show others...
2021 (English)In: MedrxivArticle in journal (Refereed) Published
Abstract [en]

More knowledge regarding persistence of antibody response to SARS-CoV-2 infections in the general population with mild symptoms is needed. We measured and compared levels of SARS CoV-2 spike- and nucleocapsid-specific IgG-antibodies in serum samples from 145 laboratory confirmed COVID-19 cases and 324 non-cases. The IgG-antibody levels against the spike protein in cases were stable over the time-period studied (14 to 256 days), while antibody levels against the nucleocapsid protein decreased over time

National Category
Infectious Medicine
Identifiers
urn:nbn:se:ri:diva-56949 (URN)10.1101/2021.06.16.21258960 (DOI)
Note

This project was exclusively funded by the Public Health Agency of Sweden via an assignment (S2020_05026) from the Ministry of Health and Social Affairs, Government of Sweden.

Available from: 2021-11-19 Created: 2021-11-19 Last updated: 2023-12-07Bibliographically approved
Choi, J., Wahlgren, M., Ek, V., Elofsson, U., Fransson, J., Nilsson, L., . . . Söderberg, C. (2020). Characterization of binding between model protein GA-Z and human serum albumin using asymmetrical flow field-flow fractionation and small angle X-ray scattering.. PLOS ONE, 15(11), Article ID e0242605.
Open this publication in new window or tab >>Characterization of binding between model protein GA-Z and human serum albumin using asymmetrical flow field-flow fractionation and small angle X-ray scattering.
Show others...
2020 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 11, article id e0242605Article in journal (Refereed) Published
Abstract [en]

Protein-based drugs often require targeted drug delivery for optimal therapy. A successful strategy to increase the circulation time of the protein in the blood is to link the therapeutic protein with an albumin-binding domain. In this work, we characterized such a protein-based drug, GA-Z. Using asymmetrical flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) we investigated the GA-Z monomer-dimer equilibrium as well as the molar binding ratio of GA-Z to HSA. Using small angle X-ray scattering, we studied the structure of GA-Z as well as the complex between GA-Z and HSA. The results show that GA-Z is predominantly dimeric in solution at pH 7 and that it binds to monomeric as well as dimeric HSA. Furthermore, GA-Z binds to HSA both as a monomer and a dimer, and thus, it can be expected to stay bound also upon dilution following injection in the blood stream. The results from SAXS and binding studies indicate that the GA-Z dimer is formed between two target domains (Z-domains). The results also indicate that the binding of GA-Z to HSA does not affect the ratio between HSA dimers and monomers, and that no higher order oligomers of the complex are seen other than those containing dimers of GA-Z and dimers of HSA.

National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-50945 (URN)10.1371/journal.pone.0242605 (DOI)33232370 (PubMedID)
Available from: 2020-12-02 Created: 2020-12-02 Last updated: 2023-12-07Bibliographically approved
Karalius, A., Zhang, Y., Kravchenko, O., Elofsson, U., Szabó, Z., Yan, M. & Ramström, O. (2020). Formation and Out-of-Equilibrium, High/Low State Switching of a Nitroaldol Dynamer in Neutral Aqueous Media. Angewandte Chemie International Edition, 59(9), 3434-3438
Open this publication in new window or tab >>Formation and Out-of-Equilibrium, High/Low State Switching of a Nitroaldol Dynamer in Neutral Aqueous Media
Show others...
2020 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 59, no 9, p. 3434-3438Article in journal (Refereed) Published
Abstract [en]

The nitroaldol reaction is demonstrated as an efficient dynamic covalent reaction in phosphate buffers at neutral pH. Rapid equilibration was recorded with pyridine-based aldehydes, and dynamic oligomerization could be achieved, leading to nitroaldol dynamers of up to 17 repeating units. The dynamers were applied in a coherent stimuli-responsive molecular system in which larger dynamers transiently existed out-of-equilibrium in a neutral aqueous system rich in formaldehyde, controlled by nitromethane.

Place, publisher, year, edition, pages
Wiley-VCH Verlag, 2020
Keywords
dynamers, formaldehyde, nitroaldol, stimuli response, systems chemistry, Chemical engineering, Chemical reactions, Chemistry, Covalent reaction, Molecular systems, Out of equilibrium, Phosphate buffers, Stimuli-responsive
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-43973 (URN)10.1002/anie.201911706 (DOI)2-s2.0-85078789872 (Scopus ID)
Available from: 2020-02-17 Created: 2020-02-17 Last updated: 2023-12-07Bibliographically approved
Elofsson, U., Millqvist-Fureby, A. & Gerde, P. (2015). Pulmonary delivery of antimicrobial peptides (ed.). ONdrugDelivery, 57, 4-7
Open this publication in new window or tab >>Pulmonary delivery of antimicrobial peptides
2015 (English)In: ONdrugDelivery, ISSN 2049-145X, Vol. 57, p. 4-7Article in journal (Refereed) Published
Abstract [en]

Anna Fureby, PhD, Group Manager & Senior Scientist, Life Science, and Ulla Elofsson, PhD, Senior Scientist, both of SP Technical Research Institute of Sweden, and Per Gerde, PhD, Chief Scientific Officer, Inhalation Sciences Sweden, discuss the serious problem of antibiotic resistance and the potential role of antimicrobial peptides in the treatment of resistant bacterial strains. For pulmonary infections, optimising the formulation and delivery method is a crucial factor for success.

National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-27361 (URN)2-s2.0-84930504376 (Scopus ID)
Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2023-12-07Bibliographically approved
Lundin, M., Elofsson, U., Blomberg, E. & Rutland, M. W. (2010). Adsorption of lysozyme, beta-casein and their layer-by-layer formation on hydrophilic surfaces: Effect of ionic strength (ed.). Colloids and Surfaces B: Biointerfaces, 77(1), 1-11
Open this publication in new window or tab >>Adsorption of lysozyme, beta-casein and their layer-by-layer formation on hydrophilic surfaces: Effect of ionic strength
2010 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 77, no 1, p. 1-11Article in journal (Refereed) Published
Abstract [en]

The adsorbed amount and layer structure of lysozyme, _x0002_-casein and mixed layers of the two proteins were studied on hydrophilic silica and quartz surfaces using the following techniques: ellipsometry, quartz crystal microbalance with dissipation monitoring (QCM-D) and total internal reflection fluorescence (TIRF). Particular emphasis was put on the effect of solution ionic strength on the layer formation. Both lysozyme and _x0002_-casein showed a higher affinity for the silica surface when adsorbed from a solution of low ionic strength even though _x0002_-casein and silica are negatively charged at the pH used. No _x0002_-casein remained adsorbed after rinsing with a 150mMbuffer solution. The adsorbed amount of lysozyme on silica exceeded a monolayer coverage irrespective of the solution conditions and displayed a rigid structure. _x0002_-Casein forms more than a single layer on pre-adsorbed lysozyme; an inner flat layer and an outer layer with an extended structure, which largely desorbs on rinsing. The build-up through sequential adsorption of lysozyme and _x0002_-casein is favoured at intermediate and high ionic strength. The total adsorbed amount increased slightly with each deposition cycle and the mixed lysozyme/_x0002_-casein layers contain higher amounts of protein compared to those of pure lysozyme or _x0002_-casein. Sequential adsorption gives rise to a proteinaceous layer consisting of both lysozyme and _x0002_-casein. The protein layers are probably highly interpenetrated with no clear separation between them.

Keywords
Adsorption of lysozyme, beta-casein and their layer-by-layer formation on hydrophilic surfaces: Effect of ionic strength, Lysozyme, [Beta- ]Casein, Layer-by-layer, Protein adsorption, Multilayers, Ellipsometry, QCM-D, TIRF, Solvent content
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-26387 (URN)10.1016/j.colsurfb.2009.12.019 (DOI)
Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2023-12-07Bibliographically approved
Sonesson, A., Callisen, T., Elofsson, U. & Brismar, H. (2008). Adsorption and activity of Thermomyces lanuginosus lipase on hydrophobic and hydrophilic surfaces measured with dual polarization interferometry (DPI) and confocal microscopy (ed.). Colloids and Surfaces B: Biointerfaces, 61, 208-215
Open this publication in new window or tab >>Adsorption and activity of Thermomyces lanuginosus lipase on hydrophobic and hydrophilic surfaces measured with dual polarization interferometry (DPI) and confocal microscopy
2008 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 61, p. 208-215Article in journal (Refereed) Published
Abstract [en]

The adsorption and activity of Thermomyces lanuginosus lipase (TLL) was measured with dual polarization interferometry (DPI) and confocal microscopy at a hydrophilic and hydrophobic surface. In the adsorption isotherms, it was evident that TLL both had higher affinity for the hydrophobic surface and adsorbed to a higher adsorbed amount (1.90 mg/m2) compared to the hydrophilic surface (1.40–1.50 mg/m2). The thickness of the adsorbed layer was constant (not, vert, similar3.5 nm) on both surfaces at an adsorbed amount >1.0 mg/m2, but decreased on the hydrophilic surface at lower surface coverage, which might be explained by partially unfolding of the TLL structure. However, a linear dependence of the refractive index of the adsorbed layer on adsorbed amount of TLL on C18 surfaces indicated that the structure of TLL was similar at low and high surface coverage. The activity of adsorbed TLL was measured towards carboxyfluorescein diacetate (CFDA) in solution, which upon lipase activity formed a fluorescent product. The surface fluorescence intensity increase was measured in a confocal microscope as a function of time after lipase adsorption. It was evident that TLL was more active on the hydrophilic surface, which suggested that a larger fraction of adsorbed TLL molecules were oriented with the active site facing the solution compared to the hydrophobic surface. Moreover, most of the activity remained when the TLL surface coverage decreased. Earlier reports on TLL surface mobility on the same surfaces have found that the lateral diffusion was highest on hydrophilic surfaces and at low surface coverage of TLL. Hence, a high lateral mobility might lead to a longer exposure time of the active site towards solution, thereby increasing the activity against a water-soluble substrate.

Keywords
Thermomyces lanuginosus lipase, protein adsorption, activity, dual polarization interferometry, confocal microscopy
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-26481 (URN)
Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2023-12-07Bibliographically approved
Sonesson, A., Blom, H., Hassler, K., Elofsson, U., Callisen, T. & Widengren, J. (2008). Protein-surfactant interactions at hydrophobic interfaces studied with total internal reflection fluorescence correlation spectroscopy (TIR-FCS) (ed.). Journal of Colloid and Interface Science, 317(2), 449-457
Open this publication in new window or tab >>Protein-surfactant interactions at hydrophobic interfaces studied with total internal reflection fluorescence correlation spectroscopy (TIR-FCS)
Show others...
2008 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 317, no 2, p. 449-457Article in journal (Refereed) Published
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-26663 (URN)
Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2023-12-07Bibliographically approved
Svendsen, I., Lindh, L., Elofsson, U. & Arnebrant, T. (2008). Studies on the exchange of early pellicle proteins by mucin and whole saliva (ed.). Journal of Colloid and Interface Science, 321(1), 52-59
Open this publication in new window or tab >>Studies on the exchange of early pellicle proteins by mucin and whole saliva
2008 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 321, no 1, p. 52-59Article in journal (Refereed) Published
Abstract [en]

Adsorption of small pellicle proteins statherin or proline-rich protein 1 (PRP1), respectively, and subsequent adsorption of human whole saliva (HWS) or salivary mucin MUC5B, respectively, was studied using ellipsometry and total internal reflectance fluorescence. Differences in elution (using sodium dodecyl sulphate (SDS) solutions) between mixed and single protein films were also investigated. On both hydrophilic and hydrophobized surfaces HWS and MUC5B were found to adsorb to pre-adsorbed layers of statherin and PRP1, respectively. Statherin adsorption on both substrate types showed no or minor exchange by HWS or MUC5B and no change in SDS elution between mixed and single protein films. Small amounts of PRP1 were exchanged by HWS on both surface types and the SDS elutable fractions were similar or larger for mixed films compared to single protein films. PRP1 and MUC5B in sequence showed minor exchange of PRP1 on hydrophilic surfaces, while no exchange could be established on hydrophobized substrates. SDS elutable fractions decreased for PRP1 and MUC5B mixed films compared to single protein films. In conclusion, minor amounts of statherin and PRP1 are exchanged during the time course of the experiments, which indicates that these proteins may to a large extent remain incorporated in the pellicle.

Keywords
Total internal reflectance fluorescence, Ellipsometry, Hydrophilic surfaces, Hydrophobic surfaces, FITC, SDS, MUC5B, Proline-rich protein, Statherin
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-26665 (URN)
Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2023-12-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3350-0242

Search in DiVA

Show all publications