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Millqvist-Fureby, AnnaORCID iD iconorcid.org/0000-0001-9891-8968
Alternative names
Publications (10 of 56) Show all publications
Osanlóo, D. T., Mahlin, D., Bjerregaard, S., Bergenståhl, B. & Millqvist-Fureby, A. (2024). Formulation factors affecting foam properties during vacuum foam-drying. International Journal of Pharmaceutics, 652, Article ID 123803.
Open this publication in new window or tab >>Formulation factors affecting foam properties during vacuum foam-drying
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2024 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 652, article id 123803Article in journal (Refereed) Published
Abstract [en]

This paper explores how vacuum foam-drying of a protein is influenced by formulation parameters by investigating the foam structure, physical properties of the foam, and the stability of the protein. Recombinant human bile salt-stimulated lipase was used as a model of a protein drug. The stability of the lipase was evaluated through activity measurements. Two disaccharides (sucrose and trehalose), strongly tending to an amorphous form, were used as matrix formers, and the physical properties were assessed through residual water content, glass transition temperature, and crystalline state. Moreover, some formulations included surfactants with different sizes and structures of the head group. The alkyl chain length was kept constant to only investigate the impact of the surfactant head group, in the presence of the lipase, on the foamability and surface coverage of the lipase. The study demonstrated that the lipase allowed for a dry, solid foam with a foam overrun of up to 2600 %. The wall thickness of the dry, solid foam was estimated to be 20–50 µm. Clear differences between sucrose and trehalose as matrix former were identified. The lipase showed no tendency to lose activity because of the drying and rehydration, despite a proportion of the lipase covering the surfaces of the dry material. 

Place, publisher, year, edition, pages
Elsevier B.V., 2024
Keywords
Lipase, Matrix former, Protein formulations, Solid-state properties, Surface composition, Vacuum foam-drying
National Category
Chemical Engineering
Identifiers
urn:nbn:se:ri:diva-71913 (URN)10.1016/j.ijpharm.2024.123803 (DOI)2-s2.0-85184501646 (Scopus ID)
Funder
Vinnova, 2018-04730
Note

'Correspondence Address: D. Tristan Osanlóo; RISE Research Institutes of Sweden, Stockholm, Box 5604, SE-114 86, Sweden; The authors would like to thank Swedish Orphan Biovitrum for providing the lipase and Croda Nordica AB for the delivery of the surfactants. Dr. Stefan Ulvenlund (ENZA Biotech AB) is gratefully acknowledged for the delivery of surfactants and valuable discussions. This research was funded by the Swedish Governmental Agency for Innovation Systems (VINNOVA) and was carried out within the competence center NextBioForm (grant number 2018-04730).

Available from: 2024-02-22 Created: 2024-02-22 Last updated: 2024-02-22Bibliographically approved
Stenlund, P., Enstedt, L., Gilljam, K., Standoft, S., Ahlinder, A., Lundin Johnson, M., . . . Berglin, M. (2023). Development of an All-Marine 3D Printed Bioactive Hydrogel Dressing for Treatment of Hard-to-Heal Wounds. Polymers, 15(12), Article ID 2627.
Open this publication in new window or tab >>Development of an All-Marine 3D Printed Bioactive Hydrogel Dressing for Treatment of Hard-to-Heal Wounds
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2023 (English)In: Polymers, E-ISSN 2073-4360, Vol. 15, no 12, article id 2627Article in journal (Refereed) Published
Abstract [en]

Current standard wound care involves dressings that provide moisture and protection; however, dressings providing active healing are still scarce and expensive. We aimed to develop an ecologically sustainable 3D printed bioactive hydrogel-based topical wound dressing targeting healing of hard-to-heal wounds, such as chronic or burn wounds, which are low on exudate. To this end, we developed a formulation composed of renewable marine components; purified extract from unfertilized salmon roe (heat-treated X, HTX), alginate from brown seaweed, and nanocellulose from tunicates. HTX is believed to facilitate the wound healing process. The components were successfully formulated into a 3D printable ink that was used to create a hydrogel lattice structure. The 3D printed hydrogel showed a HTX release profile enhancing pro-collagen I alpha 1 production in cell culture with potential of promoting wound closure rates. The dressing has recently been tested on burn wounds in Göttingen minipigs and shows accelerated wound closure and reduced inflammation. This paper describes the dressings development, mechanical properties, bioactivity, and safety. 

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
3D printed scaffolds, alginate, biomaterial, hard-to-heal wounds, nanocellulose, salmon roe, wound dressing, 3D printing, Biomechanics, Cell culture, Hydrogels, %moisture, 'current, 3d printed scaffold, Bioactive hydrogels, Hard-to-heal wound, Hydrogels dressings, Nano-cellulose, Wound closure, Wound dressings
National Category
Biomaterials Science
Identifiers
urn:nbn:se:ri:diva-65731 (URN)10.3390/polym15122627 (DOI)2-s2.0-85163772755 (Scopus ID)
Note

Correspondence Address: P. Stenlund; Department of Methodology, Textile and Medical Technology, RISE Research Institutes of Sweden AB, Gothenburg, Arvid Wallgrens backe 20, SE-413 46, Sweden;  This research was funded by ERA-Net Cofund on the Blue Bioeconomy—Unlocking the Potential of Aquatic Bioresources (BlueBio ID: 151), Swedish Research Council for Environment Agricultural Sciences and Spatial Planning (2019-02350), and Norwegian Research Council (311702).

Available from: 2023-08-08 Created: 2023-08-08 Last updated: 2024-04-02Bibliographically approved
Osanloo, D., Fransson, J., Bergenståhl, B. & Millqvist-Fureby, A. (2023). Effects of drying methods on physical properties and morphology of trehalose/mannitol mixtures. Drying Technology, 41(4), 503-522
Open this publication in new window or tab >>Effects of drying methods on physical properties and morphology of trehalose/mannitol mixtures
2023 (English)In: Drying Technology, ISSN 0737-3937, E-ISSN 1532-2300, Vol. 41, no 4, p. 503-522Article in journal (Refereed) Published
Abstract [en]

Solid-state properties of dried protein formulations are important for stability and functionality of the product. This study investigates how different drying technologies (freeze-drying with and without annealing, spray drying and spray-freeze drying) affect the structure and solid-state properties of a set of matrix formulations composed of trehalose (glass former) and mannitol (scaffolding agent) in five ratios. The dried materials were characterized using differential scanning calorimetry, thermogravimetric analysis, x-ray diffraction and scanning electron microscopy. The morphology of the dried matrix is determined by the drying technology and the composition. In all mixtures, mannitol partially dissolved in the amorphous trehalose, resulting in reduced glass transition temperature. At least 50% mannitol is required to achieve a scaffolding effect through crystallized mannitol. At 25% mannitol poor structural stability is obtained regardless of drying technology. Despite the vast differences in drying kinetics, all drying technologies resulted in similar amorphous content in the dried material. © 2022 The Author(s). 

Place, publisher, year, edition, pages
Taylor and Francis Ltd., 2023
Keywords
Freeze-drying, morphology, scaffolding, solid-state, spray drying, spray-freeze drying, Differential scanning calorimetry, Drug products, Glass, Glass transition, Mixtures, Polyols, Scanning electron microscopy, Stability, Thermogravimetric analysis, Drying methods, Drying technology, Freeze drying, Physical morphology, Protein formulation, Solid-state properties, Spray freeze drying, Spray-drying
National Category
Cell Biology
Identifiers
urn:nbn:se:ri:diva-60065 (URN)10.1080/07373937.2022.2103564 (DOI)2-s2.0-85135627393 (Scopus ID)
Note

This research was funded by Swedish Governmental Agency for Innovation Systems (VINNOVA) and was carried out within the NexBioForm Competence Centre.

Available from: 2022-09-05 Created: 2022-09-05 Last updated: 2023-11-03Bibliographically approved
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
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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
Bogdanova, E., Lages, S., Phan-Xuan, T., Kamal, M. A., Terry, A., Millqvist-Fureby, A. & Kocherbitov, V. (2023). Lysozyme-Sucrose Interactions in the Solid State: Glass Transition, Denaturation, and the Effect of Residual Water. Molecular Pharmaceutics
Open this publication in new window or tab >>Lysozyme-Sucrose Interactions in the Solid State: Glass Transition, Denaturation, and the Effect of Residual Water
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2023 (English)In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392Article in journal (Refereed) Epub ahead of print
Abstract [en]

The freeze-drying of proteins, along with excipients, offers a solution for increasing the shelf-life of protein pharmaceuticals. Using differential scanning calorimetry, thermogravimetric analysis, sorption calorimetry, and synchrotron small-angle X-ray scattering (SAXS), we have characterized the properties at low (re)hydration levels of the protein lysozyme, which was freeze-dried together with the excipient sucrose. We observe that the residual moisture content in these samples increases with the addition of lysozyme. This results from an increase in equilibrium water content with lysozyme concentration at constant water activity. Furthermore, we also observed an increase in the glass transition temperature (Tg) of the mixtures with increasing lysozyme concentration. Analysis of the heat capacity step of the mixtures indicates that lysozyme does not participate in the glass transition of the sucrose matrix; as a result, the observed increase in the Tg of the mixtures is the consequence of the confinement of the amorphous sucrose domains in the interstitial space between the lysozyme molecules. Sorption calorimetry experiments demonstrate that the hydration behavior of this formulation is similar to that of the pure amorphous sucrose, while the presence of lysozyme only shifts the sucrose transitions. SAXS analysis of amorphous lysozyme-sucrose mixtures and unfolding of lysozyme in this environment show that prior to unfolding, the size and shape of lysozyme in a solid sucrose matrix are consistent with its native state in an aqueous solution. The results obtained from our study will provide a better understanding of the low hydration behavior of protein-excipient mixtures and support the improved formulation of biologics. © 2023 The Authors. 

Place, publisher, year, edition, pages
American Chemical Society, 2023
Keywords
differential scanning calorimetry, glass transition, hydration, proteins, small-angle X-ray scattering, solid-state formulations
National Category
Physical Chemistry
Identifiers
urn:nbn:se:ri:diva-66144 (URN)10.1021/acs.molpharmaceut.3c00403 (DOI)2-s2.0-85168498460 (Scopus ID)
Note

This research was funded by the Swedish Governmental Agency for InnovationSystems (VINNOVA) and was carried out within the competence center NextBioForm.Mr. Shuai Bai (Lund University) is thanked for freeze-dryinglysozyme−sucrose samples. The SAXS measurements were performed on the CoSAXS beam lineat MAX IV (Lund,Sweden) under the proposal 20200788. The research conducted at MAXIV, a Swedish national user facility, is supported by the Swedish Research Counci lunder contract 2018-07152, the Swedish Governmental Agency for Innovation Systems under contract No. 2018-04969, and Formas under contract 2019-02496.

Available from: 2023-09-08 Created: 2023-09-08 Last updated: 2023-09-08Bibliographically approved
Palmkron, S. B., Bergenståhl, B., Håkansson, S., Wahlgren, M., Millqvist-Fureby, A. & Larsson, E. (2023). Quantification of structures in freeze-dried materials using X-ray microtomography. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 658, Article ID 130726.
Open this publication in new window or tab >>Quantification of structures in freeze-dried materials using X-ray microtomography
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2023 (English)In: Colloids and Surfaces A: Physicochemical and Engineering Aspects, ISSN 0927-7757, E-ISSN 1873-4359, Vol. 658, article id 130726Article in journal (Refereed) Published
Abstract [en]

The structure of a freeze-dried material is essential for its ability to preserve and protect biologics such as proteins, cells and other sensitive structures. The structure of a typical freeze-dried matrix can be described as pores surrounded by thin walls where the walls are the encapsulating material (for e.g. cells). The objective of this investigation is to evaluate X-ray microtomography (µCT) as a characterization method to quantifying the matrix of a freeze dried material, and compare it to scanning electron microscopy (SEM). The material consists of maltodextrin, freeze-dried below or above the glass transition temperature of the maximal freeze concentration (Tg′) and after applying annealing. The SEM images have high resolution and provide an excellent view of the sample. However, it is challenging to perform any image analysis and to ensure that a representative section is presented. The µCT images provide a rather uniform contrast between material and void, allowing for a simple grey-level thresholding when separating structure from the background. A robust image analysis procedure allows the results extracted from a representative sample volume to be evaluated. Further image analysis has been focused on understanding the thickness of the encapsulating structures by estimations of volume-weighted averages of inscribed spheres within the walls. The results show two types of structures: A large pore structure of around 20–100 µm separated by thin walls around 2–3 µm thick, and a finer structure consisting of smaller pockets of air (< 10 µm) packed in a honeycomb like structure. The structures of the samples dried below and above Tg′ have smaller and thinner structures, while material dried after annealing has larger and thicker structures. The structures display comparably small differences between the different drying protocols despite the quite different drying conditions.

Keywords
Freeze-drying, Annealing, SEM, X-ray Microtomography, µCT, Structure, Wall thickness, Pore size
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:ri:diva-62513 (URN)2-s2.0-85143725899 (DOI)
Note

This research was financed by BioGaia AB and Competence Centre NextBioForm, funded by Vinnova Swedish Governmental Agency for Innovation under grant number 2018-04730. This project also received funding from Vinnova under the call “Increasing PhD students' competence in neutron- and synchroton-based analysis methods in industry” for the project “Microtomography for in-situ investigation of freeze-drying of probiotics” under grant number 2020–00824.

The computations and data handling were carried out under the following QIM-related projects: SNIC 2022/6-157 and LU 2022/2-22, which were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at LUNARC at Lund University, partially funded by the Swedish Research Council through grant agreement no. 2018-05973.

Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2023-05-09Bibliographically approved
Gidlöf, Z., Lomstein Pedersen, B., Nilsson, L., Teleman, A., Wahlgren, M. & Millqvist-Fureby, A. (2023). Utilising phase diagram to understand barley starch microsphere preparation in an aqueous two-phase system. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 658, Article ID 130652.
Open this publication in new window or tab >>Utilising phase diagram to understand barley starch microsphere preparation in an aqueous two-phase system
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2023 (English)In: Colloids and Surfaces A: Physicochemical and Engineering Aspects, ISSN 0927-7757, E-ISSN 1873-4359, Vol. 658, article id 130652Article in journal (Refereed) Published
Abstract [en]

In this work, a waxy barley starch-PEG aqueous two-phase system (ATPS) phase diagram was constructed, and starch microsphere preparation was explored at different phase diagram positions. The aim was to investigate starch-PEG ATPS phase behaviour and relate this to starch crystallisation and microsphere formation. The hypothesis was that phase diagram position would influence the starch microsphere preparation and the properties of the microspheres. The microsphere formation process was investigated with regard to microsphere development and starch crystallisation kinetics. Microsphere physicochemical properties and their development during different stages of the preparation were studied by examining freshly produced, freeze-dried, and redispersed microspheres. Enzymatic hydrolysis of redispersed microspheres was also investigated. It was possible to produce microspheres from different positions in the phase diagram using 24 h incubation at 25 °C. However, the operational area for the used production conditions was relatively small compared to the biphasic region of the phase diagram. The main findings were that the starch-PEG ATPS phase behaviour can affect the rate of microsphere formation and particle size, but the additional properties of the dried and redispersed microspheres did not differ to a considerable extent. Thus, we have identified a robust production space where production parameters such as time to obtain microspheres can be considerably influenced by the ATPS system phase diagram position.

Keywords
Barley starch, Microspheres, Aqueous two-phase system, ATPS, Phase diagram, Starch crystallisation
National Category
Food Engineering
Identifiers
urn:nbn:se:ri:diva-62514 (URN)10.1016/j.colsurfa.2022.130652 (DOI)2-s2.0-85145556521 (Scopus ID)
Note

We acknowledge the Swedish Foundation for Strategic Research for founding of Zandra Gidlöf (Grant number FID18-0026). This research was also financed through Competence Centre NextBioForm, funded by Vinnova Swedish Governmental Agency for Innovation and The Swedish Research Council under grant number 2018-04730.

Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2023-11-03Bibliographically approved
Bogdanova, E., Millqvist-Fureby, A. & Kocherbitov, V. (2022). Influence of Cooling Rate on Ice Crystallization and Melting in Sucrose-Water System. Journal of Pharmaceutical Sciences, 111(7), 2030-2037
Open this publication in new window or tab >>Influence of Cooling Rate on Ice Crystallization and Melting in Sucrose-Water System
2022 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 111, no 7, p. 2030-2037Article in journal (Refereed) Published
Abstract [en]

The ice crystallization and melting in systems where the equilibrium state is difficult to reach is one of the growing areas in pharmaceutical freeze-drying research. The quality of the final freeze-dried product depends on the parameters of the cooling step, which affect the ice nucleation and growth. In this paper, we present a DSC study of ice crystallization and melting in a sucrose-water system. Using two different types of thermal cycles, we examine the influence of cooling and heating rates on the thermal behavior of sucrose-water solutions with water contents between 50 and 100 wt%. The DSC results show that low cooling rates provide crystallization at higher temperatures and lead to lower amount of non-freezing water. Consequently, the glass transition and ice melting properties observed upon heating depend on the cooling conditions in the preceding step. Based on the experimental results, we investigate the reasons for the existence of the two steps on DSC heating curves in sucrose-water systems: the glass transition step and the onset of ice melting. We show that diffusion of water can be the limiting factor for ice growth and melting in the sucrose-water system when the amorphous phase is in a liquid state. In particular, when the diffusion coefficient drops below 10−14 m2/sec, the ice crystals growth or melting becomes strongly suppressed even above the glass transition temperature. Understanding the diffusion limitations in the sucrose-water system can be used for the optimization of the freeze-drying protocols for proteins and probiotics. © 2022 The Authors

Place, publisher, year, edition, pages
Elsevier B.V., 2022
Keywords
Crystallization, Differential scanning calorimetry (DSC), Diffusion, Excipients, Glass transition, Sucrose
National Category
Physical Chemistry
Identifiers
urn:nbn:se:ri:diva-58785 (URN)10.1016/j.xphs.2022.01.027 (DOI)2-s2.0-85124515733 (Scopus ID)
Note

Funding text 1: This research was funded by the Swedish Governmental Agency for Innovation Systems (Vinnova) and was carried out within the competence center NextBioForm. We would like to express our gratitude for the valuable discussions and comments on the manuscript by Dr. Jonas Fransson (Nanexa AB, Sweden) who passed away in August 2021.

Available from: 2022-03-03 Created: 2022-03-03 Last updated: 2023-05-09Bibliographically approved
Palmkron, S., Gustavsson, L., Wahlgren, M., Bergensthål, B. & Millqvist-Fureby, A. (2022). Temperature and Heat Transfer Control During Freeze Drying. Effect of Vial Holders and Influence of Pressure. Pharmaceutical research, 39, 2597
Open this publication in new window or tab >>Temperature and Heat Transfer Control During Freeze Drying. Effect of Vial Holders and Influence of Pressure
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2022 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 39, p. 2597-Article in journal (Refereed) Published
Abstract [en]

Objective: A common issue of freeze drying is the inhomogeneity between samples, both in regards to water content and structure. The purpose of this study is to address this issue, and try to understand the cause of inhomogeneity in the heat transfer and sample temperature. Methods: The temperature and the heat transfer was measured using different setups, both with and without vial holders at various positions at different shelf temperature and chamber pressures. By comparing sublimation rate measurements (water sample) with temperature equilibrium measurements with a non-evaporating liquid (oil sample), the heat transfer contribution from radiation and conduction could be separated and investigated individually. Results: The oil sample temperature increases each time the pressure is decreased; the increase is highest at lower shelf temperatures. Using vial holder reduces the deviation between the samples but have limited effect on the temperature increase. The sublimation rate for water sample is pressure dependent and samples close to the walls have a higher sublimation rate than vials in the center. The sublimation rate increases slightly when using a vial holder but the deviation between vials becomes more random. Conclusions: The heat transfer consists of conduction through rectified vapor and radiation from surrounding walls, about 65–75% of the heat is transferred by conduction and 25–35% by radiation under normal operational conditions. As the vial holder is also influenced by the radiation, the vial inside the holder is indirectly affected by the surrounding radiation. © 2022, The Author(s).

Place, publisher, year, edition, pages
Springer, 2022
Keywords
freeze-frying, heat transfer, radiation, sublimation rate, vial holder
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:ri:diva-60066 (URN)10.1007/s11095-022-03353-4 (DOI)2-s2.0-85135560525 (Scopus ID)
Note

 Funding details: Vetenskapsrådet, VR, 2018-04730; Funding text 1: Open access funding provided by Lund University. This research was financed by BioGaia AB and Competence Centre NextBioForm, funded by Vinnova Swedish Governmental Agency for Innovation and The Swedish Research Council under grant number 2018-04730.

Available from: 2022-09-09 Created: 2022-09-09 Last updated: 2023-07-06Bibliographically approved
Rao, K. U., Henderson, D. I., Krishnan, N., Puthia, M., Glegola-Madejska, I., Brive, L., . . . Godaly, G. (2021). A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy. Scientific Reports, 11, Article ID 4201.
Open this publication in new window or tab >>A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy
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2021 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, article id 4201Article in journal (Refereed) Published
Abstract [en]

Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:ri:diva-52583 (URN)10.1038/s41598-021-83755-3 (DOI)2-s2.0-85101252476 (Scopus ID)
Note

Open access funding provided by Lund University. NK, IGM and BR thank the UK Medical Research Council for support in the MRC Centre for Molecular Bacteriology and Infection, Imperial College London. The research was funded by the Swedish Heart–Lung Foundation (20200378), Alfred Österlunds Foundation, Royal Physiographic Society of Lund, Swedish Research Council and European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no 604182, FORMAMP-Innovative Nanoformulation of Antimicrobial Peptides to Treat Bacterial Infectious Diseases

Available from: 2021-03-12 Created: 2021-03-12 Last updated: 2023-05-09Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-9891-8968

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