| 1. |
- Rostedt Punga, Anna, et al.
(author)
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Flodvåg av långtidssjuka covid-19-patienter väntar
- 2020
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In: Dagens Nyheter. - : Dagens Nyheter. - 1101-2447. ; , s. 5-5
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Journal article (pop. science, debate, etc.)abstract
- Hittills har sjukvård och forskning fokuserat på de som är svårt sjuka i covid-19. Samhällsspridningen i Sverige gör att även primärvården måste förbereda sig på ett stort antal patienter med komplexa och långdragna symtom. Nu publiceras en av de första vetenskapliga fallbeskrivningarna av en långtidssjuk patient, skriver forskare vid Uppsala universitet.
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| 2. |
- Tikhomirov, Evgenii
(author)
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Selective laser sintering for 3D printing of medications
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Suboptimal treatment caused by inaccurate dosing of prescribed medications is a challenging issue for the pharmaceutical industry. As a result, certain groups of patients, especially pediatric patients, may suffer from a lack of specific dosage forms, leading to potential side effects. To address this issue, various manipulation techniques are being applied, such as tablet crushing, splitting, and solution preparations. Unfortunately, these methods lack accuracy and economic efficiency.3D printing technology has been considered one of the potential solutions for manufacturing limited batch dosage forms. Dosage forms produced through 3D printing can be fabricated on demand for specific patients. Furthermore, the unique properties of these dosage forms, such as API amorphization, can be adjusted due to the high tunability of the 3D printing process. The work conducted in this thesis is dedicated to investigating the potential applications of Selective Laser Sintering (SLS) and the associated aspects of this method for manufacturing solid dosage forms.The investigations into printing parameters and formulation content enabled the establishment of correlations between these factors and the properties of the final dosage forms. Higher print temperature, Laser Power Ratio, and colorant concentration led to increased mass and hardness of the dosage forms.The polymer constitutes the major portion of the formulation in terms of mass. Consequently, various grades of polymer were examined to ascertain their chemical influence on the properties of the dosage forms. The findings revealed that the type of polymer, degree of hydrolysis, and dynamic viscosity of the polymer significantly impact both the dissolution rate and API amorphization.Utilizing FDM for printing the shell component of the drug delivery device improved its durability, whereas the SLS-printed insert resulted in a faster and adjustable dissolution rate. This experiment showcased the potential of combining the advantages of each technique to produce dosage forms with additional features.A thermal image analysis device was developed and employed to monitor temperature conditions throughout the printing process. The outcomes demonstrated that the collected data could be utilized for in-process quality control objectives and serve as a dataset for machine learning algorithms. This capability allows for real-time process monitoring, defect detection, and automated process refinement.In conclusion, a comprehensive study was conducted on the application of SLS and its limitations. This study will hopefully pave the way for further discussions and the implementation of this technology.
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| 3. |
- Afewerki, Samson, et al.
(author)
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Combined Catalysis for Engineering Bioinspired, Lignin-Based, Long-Lasting, Adhesive, Self-Mending, Antimicrobial Hydrogels
- 2020
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 14:12, s. 17004-17017
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Journal article (peer-reviewed)abstract
- The engineering of multifunctional biomaterials using a facile sustainable methodology that follows the principles of green chemistry is still largely unexplored but would be very beneficial to the world. Here, the employment of catalytic reactions in combination with biomass-derived starting materials in the design of biomaterials would promote the development of eco-friendly technologies and sustainable materials. Herein, we disclose the combination of two catalytic cycles (combined catalysis) comprising oxidative decarboxylation and quinone-catechol redox catalysis for engineering lignin-based multifunctional antimicrobial hydrogels. The bioinspired design mimics the catechol chemistry employed by marine mussels in nature. The resultant multifunctional sustainable hydrogels (1) are robust and elastic, (2) have strong antimicrobial activity, (3) are adhesive to skin tissue and various other surfaces, and (4) are able to self-mend. A systematic characterization was carried out to fully elucidate and understand the facile and efficient catalytic strategy and the subsequent multifunctional materials. Electron paramagnetic resonance analysis confirmed the long-lasting quinone-catechol redox environment within the hydrogel system. Initial in vitro biocompatibility studies demonstrated the low toxicity of the hydrogels. This proof-of-concept strategy could be developed into an important technological platform for the eco-friendly, bioinspired design of other multifunctional hydrogels and their use in various biomedical and flexible electronic applications.
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| 4. |
- Afewerki, Samson, 1985-, et al.
(author)
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In vitro high-content tissue models to address precision medicine challenges
- 2023
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In: Molecular Aspects of Medicine. - : Elsevier. - 0098-2997 .- 1872-9452. ; 91
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Journal article (peer-reviewed)abstract
- The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treatments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically representative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.
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| 5. |
- Alvebratt, Caroline
(author)
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Advanced Methods for Evaluation of the Performance of Complex Drug Delivery System
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Low oral bioavailability of drugs originating from poor aqueous solubility is a common issue in drug development. Various enabling formulations have been presented to circumvent this limitation, many making use of supersaturation. In these, the drug is delivered to the gastro-intestinal lumen in a high energy state e.g. in amorphous form or a liquid lipid vehicle. Concentrations surpassing the equilibrium solubility of the crystalline drug are achieved, which facilitate increased absorption for dissolution-rate limited compounds. Meanwhile the use of the enabling formulation can be beneficial to increase the bioavailability of poorly water-soluble drugs, in vitro evaluation of these systems remain challenging. Limited methods have also evaluated several different types of enabling formulation in the same experimental setup. The overall aim of this thesis was therefore to develop assays to study the performance of various complex drug delivery systems. In the first part, a small scale dissolution apparatus, the µDiss Profiler, was used to study drug release from drug-loaded mesoporous magnesium carbonate (MMC). A protective filter was developed to minimize particle interference on the UV-measurements, enabling studies of supersaturation from the amorphous carrier. In the second paper, lipids were adsorbed onto the MMC. A modified in vitro lipolysis setup was established and the samples were analyzed with nuclear magnetic resonance spectroscopy. A stability study of the lipid-loaded MMC was also performed. The methods developed in the first two projects provided an insight to events occurring in the intestinal lumen. The intestinal absorption has however been shown to be a complex interplay between dissolution-digestion and permeation. In the final two projects, two devices comprising of a donor (luminal) chamber and a receiver (serosal) chamber were studied (the µFLUX and the enabling absorption, ENA, device). The two chambers were separated by a semipermeable membrane (cell-based and/or phospholipid-based). A wide range of enabling formulations were evaluated in the two assays. As the exposure in the donor correlated poorly with the exposure in the receiver compartment, this emphasizes the importance of in vitro methods taking both the dissolution-digestion and permeation into account. The ENA results also predicted the in vivo performance in rats well. To conclude, several models have been established in the thesis to study the in vitro performance of enabling formulations, which will be valuable for screening of appropriate drug delivery systems.
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| 6. |
- Alvebratt, Caroline, et al.
(author)
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An in vitro dissolution–digestion–permeation assay for the study of advanced drug delivery systems
- 2020
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 149, s. 21-29
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Journal article (peer-reviewed)abstract
- Advanced drug delivery systems (ADDS) are widely explored to overcome poor aqueous solubility of orally administered drugs. However, the prediction of their in vivo performance is challenging, as in vitro models typically do not capture the interplay between processes occurring in the gut. In additions, different models are used to evaluate the different systems. We therefore present a method that allows monitoring of luminal processing (dissolution, digestion) and its interplay with permeation to better inform on the absorption of felodipine formulated as ADDS. Experiments were performed in a µFLUX-apparatus, consisting of two chambers, representing the intestinal and serosal compartment, separated by Caco-2 monolayers. During dissolution–digestion–permeation experiments, ADDS were added to the donor compartment containing simulated intestinal fluid and immobilized lipase. Dissolution and permeation in both compartments were monitored using in situ UV-probes or, when turbidity interfered the measurements, with HPLC analysis.The method showed that all ADDS increased donor and receiver concentrations compared to the condition using crystalline felodipine. A poor correlation between the compartments indicated the need for an serosal compartment to evaluate drug absorption from ADDS. The method enables medium-throughput assessment of: (i) dynamic processes occurring in the small intestine, and (ii) drug concentrations in real-time.
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| 7. |
- Alvebratt, Caroline, et al.
(author)
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In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier
- 2020
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 12:5
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Journal article (peer-reviewed)abstract
- Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.
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| 8. |
- Björklund, Håkan, et al.
(author)
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Ett aktivt svenskt värdskap för ESS är viktigare än någonsin : Regeringen måste ta ett aktivt ledarskap och säkra de extra resurser som krävs för att ESS ska bli tillgängligt för forskarsamhället och näringslivet, skriver rådgivare till ESS.
- 2022
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In: Dagens Industri. - Stockholm : Dagens Industri. ; 5/4
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Journal article (peer-reviewed)abstract
- Kriget i Ukraina visar på behovet av att det fria Europa står på egna ben och bygger sig starkt och då spelar forskning och utveckling en viktig roll. Den forskningsinfrastruktur som nu byggs i Sverige – till exempel European Spallation Source (ESS) – har stor betydelse för att vi ska behålla och utveckla vårt teknologiska ledarskap och samtidigt bidra till att lösa de stora utmaningar mänskligheten står inför. De flesta av oss vill se ett starkt och attraktivt Europa som kännetecknas av innovation, framtidstro och medmänsklighet. I en konkurrensutsatt värld behöver samhällsdebatten handla mer om hur vi skapar vårt välstånd, för det kommer inte av sig självt. Sverige har lång tradition av nyfiket uppfinnande, skickligt ingenjörskap och drivna entreprenörer. Det är så vi har skapat de svenska företag som nu är globala. Vi säljer varor och tjänster på en världsmarknad, vilket förutsätter teknologiskt ledarskap och spetskompetens. Exportnettot, handelsbalansens överskott, omvandlas till välstånd hemmavid och det går en rak linje från innovationer till äldreomsorg. Men att vara ett innovativt ledande land är en position som ständigt måste erövras. Varje dag. Efter 150 år av forskning och framsteg, tillväxt och ökande välstånd, växer mänskligheten in i en ny fas. Vi kommer att behöva leva, producera och konsumera på nya sätt. Utmaningarna är kända, men lösningarna är okända och det är bråttom. De stora frågorna har många svar och redskapen för att förflytta vår kunskaps gräns blir alltmer avancerade. Nya skräddarsydda material är väsentliga för att lösa många av utmaningarna. I industrins barndom kom ingenjörerna långt med envishet och enkla verktyg. Men de lågt hängande frukterna är plockade. De enkla lösningarna implementerade. För att kunna fortsätta krävs alltmer avancerade metoder och angreppssätt som kräver miljardinvesteringar för att studera material i dess minsta beståndsdelar och se hur celler reagerar på olika substanser. Energiutmaningen har inte en enda storskalig lösning utan behöver ständiga framsteg inom allt från processteknik till energialstring. Cancer har inte ett motmedel, utan stävjas genom många upptäckter inom allt från immunologi till radiologi. De tusen stegens innovationer avgör vår förmåga att lyckas med omställningen till ett mer hållbart samhälle och att utveckla nya behandlingsformer och botemedel. Att Sverige och svensk industri tar en ledande roll i denna utveckling borde vara självklart för alla. För drygt tjugo år sedan tog nordiska forskare initiativ till att skapa en världsledande infrastruktur för materialforskning i Sverige. Nu installeras instrumenten på ESS medan forskning redan pågår hos grannen MAX IV. ESS är en av Europas största vetenskapliga satsningar och beräknas vara i drift under 40 års tid. Sverige har fått ett guldägg i sin famn – sin första globala Big Science anläggning någonsin – och är värdland med Danmark som medvärd. Tretton av Europas mest tekniskt avancerade nationer finansierar detta tillsammans. ESS beräknas bli 20 gånger mer kraftfull än befintliga motsvarande anläggningar, vilket kommer att ge forskare tillgång till världens skarpaste ”öga” in i organisk och oorganisk materia. ESS blir ett verktyg som kan hjälpa mänskligheten att söka svar på många frågor som måste lösas inom energi, medicin, bioteknik, datalagring och -processing, ja inom alla områden som behöver smarta material. Närheten till Max IV är genomtänkt och en stor möjlighet. Anläggningarna kompletterar varandra och kommer att kunna bidra till ny banbrytande kunskap, nya innovationer och nya företag. Den forskning som kommer att bedrivas vid ESS stämmer väl med vår industriella tradition av ingenjörskap och det ständiga sökandet efter bättre produkter och processer. För Sverige innebär närvaron av ESS en exceptionell möjlighet. Tusentals spetsforskare från hela världen kommer varje år att komma till Sverige. Den förstärkning det innebär för forskarsamhälle, innovationsklimat och näringsliv är stor och kommer inte att likna något vi hittills sett. Satsningen kräver aktivt svenskt värdskap.ESS stärker Sveriges rykte som kunskapsnation, förbättrar vår konkurrenskraft och ger större möjligheter att tackla samhällsutmaningarna genom samverkan mellan näringsliv, samhälle och akademi. Det är en mycket långsiktig satsning som handlar om vårt framtida välstånd. För att få utdelning på Sveriges investering måste vi se till att svenska företag blir bäst i världen på att använda ESS. I dag finns en nationell strategi och ett kansli kopplat till Vetenskapsrådet och Vinnova, men det är bara början. Därför har vi valt att engagera oss ideellt, som rådgivare till ESS, för att stödja samarbetet mellan företag, samhälle och ESS.Ett aktivt svenskt värdskap för ESS är viktigare än någonsin. Pandemin leder till förseningar och därmed kostnadsökningar av stora och komplexa projekt som ESS, men förstärker samtidigt det långsiktiga behovet av ny kunskap. Det är ytterst viktigt att vi nu bäddar för framtiden så att ESS kommer i drift så snart som möjligt och kan bidra till att lösa de stora utmaningar vi står inför. Vi uppmanar därför regeringen att ta ett aktivt ledarskap för ESS genom att tillsammans med övriga medlemsländer säkra de extra resurser som krävs för att ESS ska bli tillgängligt för forskarsamhället och näringslivet så snart som möjligt.ESS blir världens mest kraftfulla verktyg för forskare. Håkan Björklund, styrelsearbetareArne Karlsson, styrelsearbetareLena Olving, styrelsearbetareBjörn Savén, grundare IK PartnersMaria Strömme, professor i nanoteknologiArtikelförfattarna är medlemmar i ESS Executive Advisory Board, ett rådgivande organ.
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| 9. |
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| 10. |
- Blasi-Romero, Anna, et al.
(author)
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In Vitro Investigation of Thiol-Functionalized Cellulose Nanofibrils as a Chronic Wound Environment Modulator
- 2021
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In: Polymers. - : MDPI. - 2073-4360. ; 13:2
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Journal article (peer-reviewed)abstract
- There is currently a huge need for new, improved therapeutic approaches for the treatment of chronic wounds. One promising strategy is to develop wound dressings capable of modulating the chronic wound environment (e.g., by controlling the high levels of reactive oxygen species (ROS) and proteases). Here, we selected the thiol-containing amino acid cysteine to endow wood-derived cellulose nanofibrils (CNF) with bioactivity toward the modulation of ROS levels and protease activity. Cysteine was covalently incorporated into CNF and the functionalized material, herein referred as cys-CNF, was characterized in terms of chemical structure, degree of substitution, radical scavenging capacity, and inhibition of protease activity. The stability of the thiol groups was evaluated over time, and an in vitro cytotoxicity study with human dermal fibroblasts was performed to evaluate the safety profile of cys-CNF. Results showed that cys-CNF was able to efficiently control the activity of the metalloprotease collagenase and to inhibit the free radical DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), activities that were correlated with the presence of free thiol groups on the nanofibers. The stability study showed that the reactivity of the thiol groups challenged the bioactivity over time. Nevertheless, preparing the material as an aerogel and storing it in an inert atmosphere were shown to be valid approaches to increase the stability of the thiol groups in cys-CNF. No signs of toxicity were observed on the dermal fibroblasts when exposed to cys-CNF (concentration range 0.1-0.5 mg/mL). The present work highlights cys-CNF as a promising novel material for the development of bioactive wound dressings for the treatment of chronic wounds.
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