[{"_id":"project:9209","_type":"project","abstract":{},"project_id":"2024-03851_Vinnova","identifier_short":"2024-03851","dates":{"start_date":"2025-01-01","end_date":"2029-12-31"},"organizations":[{"funding":[{"_id":94,"id":"202100-5216","sv":"Vinnova","en":"Vinnova"}]},{"coordinating":[{"_id":978,"id":"202100-2932","sv":"Uppsala universitet","en":"Uppsala University"}]}],"people":[{"project_leaders":[{"_id":"authority-person:12719","orcid":"0000-0002-8917-2612","name":"Bergström, Christel","role":"principal_investigator","affiliation":[{"_id":978,"id":"202100-2932","sv":"Uppsala universitet","en":"Uppsala University"}]}]},{"other_personnel":[]}],"tags":[],"titles":{"en":"The Swedish Drug Delivery Centre"},"total_funding":"36000000","type_of_awards":{"sv":"Projektbidrag","en":"Project grant"},"publications":[{"id":"diva2:2019835","type":"article-journal","status":"Published","issued":{"date-parts":[[2026]]},"title":"Diffusion of Affibody molecules in extracellular matrix mimetic hydrogels and the effect of albumin binding","language":"eng","author":[{"family":"Parlow","given":"Julia","ORCID":"0009-0003-1456-4288","localId":"julna760","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]},{"family":"Sandegren","given":"Anna"},{"family":"Güler","given":"Rezan"},{"family":"Karlberg","given":"Ida"},{"family":"Frejd","given":"Fredrik"},{"family":"Sjögren","given":"Helen"},{"family":"Hansson","given":"Per","ORCID":"0000-0002-0895-1180","localId":"perhanss","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]}],"abstract":"Affibody molecules are protein ligands, that due to their small size (6-19 kDa) and high target affinity exhibit favourable properties for tumour uptake valuable in diagnostic imaging and therapeutic applications. Fusion to a high affinity albumin binding domain (ABD) has been shown to improve circulatory half-life and biodistribution. However, the effect of molecular design is not obvious to predict and in vitro methods to evaluate their transport properties in physiologically relevant environment are needed. In this work we investigated the diffusivities (D) of Affibody molecules, with systematically varied molecular design, in solution and within extracellular matrix mimetic hydrogels composed of either agarose or collagen and hyaluronic acid (COL-HA) using fluorescence recovery after photobleaching. Furthermore, the effect of presence of human serum albumin (HSA) was evaluated. The correlation between D of the tested Affibody molecules in solution and their molecular weight (Mw) was weak, indicating that propensity to form reversible oligomers and the size of the oligomers are more important for their diffusion properties than Mw of the monomer. Positively charged Affibody molecules were enriched in polymer-rich domains of the COL-HA gel accompanied by a decrease in D as a result of electrostatic interactions. Binding to HSA by Affibody molecules containing an ABD was evident as a decrease of D when HSA was present. In COL-HA gels HSA-binding reduced the effect of electrostatic interactions effectively facilitating the transport of those compounds. In conclusion, molecular design especially inclusion of an ABD affected the transport properties of the tested Affibody molecules.","DOI":"10.1016/j.ijbiomac.2025.149322","PMID":"41319760","ScopusId":"2-s2.0-105023950531","NBN":"urn:nbn:se:uu:diva-572897","volume":"337","number":"149322","container-title":"International Journal of Biological Macromolecules","ISSN":"1879-0003","keyword":"Affibody molecules; Albumin-binding domain; Diffusion; Extracellular matrix; FRAP; Hydrogel; In vitro","publisher":"Elsevier","published":[{"raw":"2025-12-09T08:12:00.000+01:00"}],"created":[{"raw":"2025-12-09T08:12:27.370+01:00"}],"updated":[{"raw":"2026-01-15T16:17:45.134+01:00"}],"URL":"https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-572897"},{"id":"diva2:2017917","type":"article-journal","status":"Published","issued":{"date-parts":[[2026]]},"title":"Structural determination of self-assembled aggregates formed by a therapeutic cyclical peptide and an ionic surfactant in aqueous solution","language":"eng","author":[{"family":"Brunzell","given":"Ellen","ORCID":"0009-0002-2561-1513","localId":"ellbr290","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]},{"family":"Kim Högström","given":"Yumi","ORCID":"0009-0002-8879-277X","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]},{"family":"López Hernández","given":"Marcos"},{"family":"Skov Pedersen","given":"Jan"},{"family":"Bergström","given":"L. Magnus","ORCID":"0000-0002-3942-5730","localId":"maber499","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]}],"abstract":"Amphiphilic compounds, such as phospholipids or surface-active substances, are present in biological systems and can be part of pharmaceutical formulations. As a consequence, all pharmaceutically active ingredients will encounter amphiphilic compounds, either in the formulation or after administration. With the growing interest in peptide-based pharmaceuticals, there is a need to enhance the understanding of the interactions between peptides and amphiphilic compounds.In this particular study, we have chosen to study mixtures of the comparatively small cyclical octapeptide lanreotide and the conventional anionic surfactant sodium dodecylsulfate (SDS). This was done by examining the self-assembly structures formed in lanreotide-SDS mixtures using light scattering and small-angle X-ray scattering (SAXS).Above the critical micelle concentration (cmc) of SDS, the large excess of SDS could solubilize all lanreotide and form small micelles with lanreotide attached to the interface. Upon dilution to concentrations below the cmc of SDS, a suspension with dispersed solid nanoparticles is formed. The solid nanoparticles grow in size with decreasing concentration and, eventually, precipitate. The precipitated material is arranged in a liquid crystalline micellar phase, consisting of small close-packed SDS micelles with peptide adsorbed at the interface.We were able to conclude that lanreotide does not form mixed micelles with SDS, indicating that it lacks the amphiphilic properties required to integrate fully with SDS behaving as a cosurfactant. In contrast, lanreotide attaches to the interface of SDS micelles, resembling the interactions of polymers, proteins, and nucleic acids with surfactants.","DOI":"10.1016/j.jcis.2025.139373","ScopusId":"2-s2.0-105020786645","NBN":"urn:nbn:se:uu:diva-572391","volume":"704","number":"139373","container-title":"Journal of Colloid and Interface Science","ISSN":"1095-7103","keyword":"Self-assembly; Peptide; Surfactant; Small-angle; X-ray scattering","publisher":"Elsevier","published":[{"raw":"2025-12-01T19:01:00.000+01:00"}],"created":[{"raw":"2025-12-01T19:01:03.429+01:00"}],"updated":[{"raw":"2025-12-09T09:30:47.481+01:00"}],"URL":"https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-572391"},{"id":"diva2:2004712","type":"article-journal","status":"Published","issued":{"date-parts":[[2025]]},"title":"Diffusion of macromolecules in extracellular matrix mimetic hydrogels : effect of size and charge","language":"eng","author":[{"family":"Parlow","given":"Julia","ORCID":"0009-0003-1456-4288","localId":"julna760","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]},{"family":"Pet","given":"Eva","affiliation":[{"id":"1322","name":"Uppsala universitet, Institutionen för läkemedelskemi"}]},{"family":"Smirnova","given":"Anna","affiliation":[{"id":"1322","name":"Uppsala universitet, Institutionen för läkemedelskemi"}]},{"family":"Mojumdar","given":"Enamul","ORCID":"0000-0003-1482-7394","affiliation":[{"id":"1322","name":"Uppsala universitet, Institutionen för läkemedelskemi"}]},{"family":"Sjögren","given":"Helen","affiliation":[{"name":"Ferring Pharmaceut A S, Amager Strandvej 405, DK-2770 Kastrup, Denmark."}]},{"family":"Hansson","given":"Per","ORCID":"0000-0002-0895-1180","localId":"perhanss","affiliation":[{"id":"890402","name":"Uppsala universitet, Farmaceutisk fysikalisk kemi"}]}],"abstract":"Subcutaneous (SC) injection is the primary alternative to oral administration for therapeutic proteins and peptides. However, bioavailability and absorption rate are often variable and difficult to predict. Therefore, there is a need for new biorelevant and predictive SC in vitro methods. In this study we systematically investigate the effect of size and charge of a macromolecule on its partitioning and diffusion within extracellular matrix (ECM) mimetic hydrogels in order to gain insight on interactions with the components of the ECM affecting the absorption of a drug after SC injection. Hydrogels consisting of either agarose, cross-linked collagen and hyaluronic acid (HA) or cross-linked HA, were made and equilibrated in solutions of FITC-dextrans of varying sizes (4 to 150 kDa) and model peptides of varying net charge (+2 to +9). Partitioning and diffusion coefficients within gel and solution were determined using confocal laser scanning microscopy and fluorescence recovery after photo bleaching (FRAP), and compared to theoretical models. Generally, the partitioning and diffusivities within the gels decreased with increasing molecular weight, which was in good agreement with models describing the effect of obstruction of the gel network corrected for heterogeneity in the gel structure. The cationic peptides were enriched in the oppositely charged gels and their diffusivities decreased with increasing peptide charge. The experimental results were in semi quantitative agreement with an electrostatic model presented in this work.","DOI":"10.1016/j.ejps.2025.107257","PMID":"40914464","ScopusId":"2-s2.0-105015175388","NBN":"urn:nbn:se:uu:diva-568656","volume":"214","number":"107257","container-title":"European Journal of Pharmaceutical Sciences","ISSN":"1879-0720","keyword":"Peptide; Diffusion; Extracellular matrix; In vitro; Subcutaneous; FRAP","publisher":"Elsevier","published":[{"raw":"2025-10-08T10:32:41.495+02:00"}],"created":[{"raw":"2025-10-08T10:32:41.563+02:00"}],"updated":[{"raw":"2025-12-09T09:51:36.418+01:00"}],"URL":"https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-568656"},{"id":"diva2:1967093","type":"article-journal","status":"Published","issued":{"date-parts":[[2025]]},"title":"Optimized Artificial Colonic Mucus Enabling Physiologically Relevant Diffusion Studies of Drugs, Particles, and Delivery Systems","language":"eng","author":[{"family":"Tjakra","given":"Marco","ORCID":"0000-0003-2266-4011","localId":"martj249","affiliation":[{"id":"1321","name":"Uppsala universitet, Institutionen för farmaci"}]},{"family":"Chakrapeesirisuk","given":"Nopdanai","affiliation":[{"id":"1321","name":"Uppsala universitet, Institutionen för farmaci"}]},{"family":"Jacobson","given":"Magdalena","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7054, SE-750 07 Uppsala, Sweden"}]},{"family":"Sellin","given":"Mikael E.","ORCID":"0000-0002-8355-0803","localId":"mikse125","affiliation":[{"id":"9051","name":"Uppsala universitet, Science for Life Laboratory, SciLifeLab"},{"id":"890408","name":"Uppsala universitet, Infektioner och Immunitet"}]},{"family":"Eriksson","given":"Jens","ORCID":"0000-0002-8945-2665","localId":"jeeri205","affiliation":[{"id":"890408","name":"Uppsala universitet, Infektioner och Immunitet"}]},{"family":"Teleki","given":"Alexandra","ORCID":"0000-0001-6514-8960","localId":"alete368","affiliation":[{"id":"1321","name":"Uppsala universitet, Institutionen för farmaci"},{"id":"9051","name":"Uppsala universitet, Science for Life Laboratory, SciLifeLab"}]},{"family":"Bergström","given":"Christel A. S.","ORCID":"0000-0002-8917-2612","localId":"cjo29958","affiliation":[{"id":"1321","name":"Uppsala universitet, Institutionen för farmaci"}]}],"abstract":"Development of oral drug delivery systems that penetrate the colonic mucus remains challenging. Artificial models of porcine colonic mucus have been developed that mimic the rheology and viscosity of the native mucus and its contents of mucins, protein, and lipids. However, they are less representative with regard to the zeta potential, a factor of importance for charged molecules and particles. This study therefore aimed to improve the existing porcine artificial colonic mucus model by exchanging the polymer backbone (used for viscosity) to more closely mimic the charge of porcine native colonic mucus. Polymers studied were poly(acrylic acid), hydroxyethylcellulose, sodium hyaluronate, sodium alginate, and pectin. The resulting porcine artificial colonic mucus was assayed for apparent viscosity, storage modulus, pH, water content, zeta potential, and pore size. The two best-performing polymers (poly(acrylic acid) and hydroxyethylcellulose) were then assayed with diffusion of FITC-dextran, particle tracking of nanoparticles, and binding of FITC-dextran and contrasted to data generated in porcine native colonic mucus (PNCM). Of the two polymers, PACM based on HEC generated zeta potential and binding kinetics similar to those of PNCM. We conclude that the choice of polymer in PACMs is critical for improving their use in drug development. The extensive characterization of the PACMs further points toward the importance of complementary techniques to determine rheological characteristics, mesh, and pore size.","DOI":"10.1021/acs.molpharmaceut.5c00298","PMID":"40492464","ScopusId":"2-s2.0-105008012035","NBN":"urn:nbn:se:uu:diva-559042","issue":"7","volume":"22","page":"4032-4045","container-title":"Molecular Pharmaceutics","ISSN":"1543-8392","keyword":"mucus; hydrogel; drug; diffusion; rheology; binding; structure; drug delivery; colon","publisher":"American Chemical Society (ACS)","published":[{"raw":"2025-06-11T10:33:00.000+02:00"}],"created":[{"raw":"2025-06-11T10:33:17.258+02:00"}],"updated":[{"raw":"2025-10-20T14:29:10.292+02:00"}],"URL":"https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-559042"}],"links":[{"type":"pid","link":"https://uu.diva-portal.org/smash/api/project/swecris/project:9209"}]}]