Change search
Link to record
Permanent link

Direct link
BETA
Publications (5 of 5) Show all publications
Nilebäck, L., Widhe, M., Seijsing, J., Bysell, H., Sharma, P. K. & Hedhammar, M. (2019). Bioactive Silk Coatings Reduce the Adhesion of Staphylococcus aureus while Supporting Growth of Osteoblast-like Cells.. ACS Applied Materials and Interfaces
Open this publication in new window or tab >>Bioactive Silk Coatings Reduce the Adhesion of Staphylococcus aureus while Supporting Growth of Osteoblast-like Cells.
Show others...
2019 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252Article in journal (Refereed) Epub ahead of print
Abstract [en]

Orthopedic and dental implants are associated with a substantial risk of failure due to biomaterial-associated infections and poor osseointegration. To prevent such outcomes, a coating can be applied on the implant to ideally both reduce the risk of bacterial adhesion and support establishment of osteoblasts. We present a strategy to construct dual-functional silk coatings with such properties. Silk coatings were made from a recombinant partial spider silk protein either alone (silkwt) or fused with a cell-binding motif derived from fibronectin (FN-silk). The biofilm-dispersal enzyme Dispersin B (DspB) and two peptidoglycan degrading endolysins, PlySs2 and SAL-1, were produced recombinantly. A sortase recognition tag (SrtTag) was included to allow site-specific conjugation of each enzyme onto silkwt and FN-silk coatings using an engineered variant of the transpeptidase Sortase A (SrtA*). To evaluate bacterial adhesion on the samples, Staphylococcus aureus was incubated on the coatings and subsequently subjected to live/dead staining. Fluorescence microscopy revealed a reduced number of bacteria on all silk coatings containing enzymes. Moreover, the bacteria were mobile to a higher degree, indicating a negative influence on the bacterial adhesion. The capability to support mammalian cell interactions was assessed by cultivation of the osteosarcoma cell line U-2 OS on dual-functional surfaces, prepared by conjugating the enzymes onto FN-silk coatings. U-2 OS cells could adhere to silk coatings with enzymes and showed high spreading and viability, demonstrating good cell compatibility.

Keywords
Staphylococcus aureus, antibacterial, endolysin, multifunctional coating, osseointegration, recombinant spider silk
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-39355 (URN)10.1021/acsami.9b05531 (DOI)31241302 (PubMedID)
Available from: 2019-07-08 Created: 2019-07-08 Last updated: 2019-07-08Bibliographically approved
Valente, F., Bysell, H., Simoni, E., Boge, L., Eriksson, M., Martini, A. & Astolfi, L. (2018). Evaluation of toxicity of glycerol monooleate nanoparticles on PC12 cell line.. International Journal of Pharmaceutics, 539(1-2), 23-30, Article ID S0378-5173(18)30054-1.
Open this publication in new window or tab >>Evaluation of toxicity of glycerol monooleate nanoparticles on PC12 cell line.
Show others...
2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 539, no 1-2, p. 23-30, article id S0378-5173(18)30054-1Article in journal (Refereed) Published
Abstract [en]

An innovative approach to improve drug delivery is the use of glycerol monooleate nanoparticles. Numerous studies describe their high versatility, low toxicity and ability to carry relatively high loads of conjugated compounds including scarcely soluble ones, providing sustained drug release and increasing drug diffusion and half-life. Despite a growing interest in their potential use for therapeutic applications, there are surprisingly few literature data concerning the toxic effects of these nanoparticles at high concentrations in vitro and in vivo, and their effects on cell metabolism. We produced and characterized from a physical-chemical point of view glycerol monooleate nanoparticles and tested them on the PC12 cell line, a rat model of neuronal differentiation. The toxicity of these nanoparticles was evaluated by molecular methods on cell viability, cell cycle, nanoparticle uptake and induction of apoptosis. The results showed that glycerol monooleate nanoparticles up to 100 μg/mL had no toxic effects on PC12 cells, did not induce significant changes in the cell cycle nor cause apoptosis. The nanoparticles entered PC12 cells 8 h after treatment, successfully delivering the conjugate compound inside cells. Overall, glycerol monooleate nanoparticles did not exhibit significant toxicity on PC12 cell line in concentrations up to 100 µg/mL, supporting their therapeutic use as drug delivery systems.

Keywords
Apoptosis, Nanoparticle, PC12 cell line, Toxicity
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-33340 (URN)10.1016/j.ijpharm.2018.01.035 (DOI)29366940 (PubMedID)2-s2.0-85041522082 (Scopus ID)
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2019-06-27Bibliographically approved
Boge, L., Västberg, A., Umerska, A., Bysell, H., Eriksson, J., Edwards, K., . . . Andersson, M. (2018). Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide. Journal of Colloid and Interface Science, 522, 126-135
Open this publication in new window or tab >>Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide
Show others...
2018 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 522, p. 126-135Article in journal (Refereed) Published
Abstract [en]

Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are receiving more and more attraction as drug delivery vehicles. Dry powder formulation that forms LCNPs upon hydration can be advantageous to make new routes of administration accessible. In this work, we investigate use of three disaccharides (lactose, trehalose and sucrose) as protective matrices for glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase behavior, particle size and size distributions at the different preparation steps were monitored by small angle x-ray scattering (SAXS) and dynamic light scattering (DLS). Particle appearance was imaged by cryogenic transmission electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial peptide AP114 (plectasin derivative) was incorporated in the formulations. Peptide encapsulation and release as well as in vitro antibacterial effect were investigated. Results showed that all freeze-dried powders did form particles with liquid crystalline structure upon hydration. However, a phase transition from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a consequence of sugar addition and the freeze-drying procedure. Data indicates that trehalose is the preferred choice of lyo-protectant in order to maintain a mono-modal particle size distribution. In addition, antimicrobial activity of AP114-containing formulations was found to be highest for the formulation containing trehalose. The release kinetics of AP114 from the nanoparticles was strongly affected by the dimensions of the hexagonal phase. Larger dimension of the hexagonal phase, significantly improved the release of AP114 and antimicrobial activity of the formulation.

Keywords
Antimicrobial peptide, AP114, Cubosome, Freeze-drying, Glycerol monooleate, Hexosome, Liquid crystal, Plectasin, Drying, Dynamic light scattering, Glycerol, High resolution transmission electron microscopy, Hydration, Liquid crystals, Low temperature drying, Microorganisms, Nanoparticles, Particle size, Particle size analysis, Peptides, Powders, Size distribution, Targeted drug delivery, Transmission electron microscopy, X ray scattering, Cubosomes, Freeze drying, Controlled drug delivery, ap 114, disaccharide, lactose, nanoparticle, polypeptide antibiotic agent, sucrose, trehalose, unclassified drug, Article, bactericidal activity, drug delivery system, drug formulation, drug release, in vitro study, kinetics, molecular stability, nonhuman, phase transition, photon correlation spectroscopy, powder, priority journal, X ray crystallography
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-34070 (URN)10.1016/j.jcis.2018.03.062 (DOI)2-s2.0-85044472786 (Scopus ID)
Available from: 2018-07-06 Created: 2018-07-06 Last updated: 2018-08-15Bibliographically approved
Boge, L., Bysell, H., Ringstad, L., Wennman, D., Umerska, A., Cassisa, V., . . . Andersson, M. (2016). Lipid-based liquid crystals as carriers for antimicrobial peptides: Phase behavior and antimicrobial effect. Langmuir, 32(17), 4217-4228
Open this publication in new window or tab >>Lipid-based liquid crystals as carriers for antimicrobial peptides: Phase behavior and antimicrobial effect
Show others...
2016 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 32, no 17, p. 4217-4228Article in journal (Refereed) Published
Abstract [en]

The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, ζ-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
National Category
Physical Chemistry Pharmaceutical Sciences
Identifiers
urn:nbn:se:ri:diva-141 (URN)10.1021/acs.langmuir.6b00338 (DOI)2-s2.0-84968912179 (Scopus ID)
Available from: 2016-06-07 Created: 2016-06-07 Last updated: 2019-06-17Bibliographically approved
Matougui, N., Boge, L., Groo, A.-C., Umerska, A., Ringstad, L., Bysell, H. & Saulnier, P. (2016). Lipid-based nanoformulations for peptide delivery. International Journal of Pharmaceutics, 502(1-2), 80-97
Open this publication in new window or tab >>Lipid-based nanoformulations for peptide delivery
Show others...
2016 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 502, no 1-2, p. 80-97Article, review/survey (Refereed) Published
Abstract [en]

Nanoformulations have attracted a lot of attention because of their size-dependent properties. Among the array of nanoformulations, lipid nanoformulations (LNFs) have evoked increasing interest because of the advantages of their high degree of biocompatibility and versatility. The performance of lipid nanoformulations is greatly influenced by their composition and structure. Therapeutic peptides represent a growing share of the pharmaceutical market. However, the main challenge for their development into commercial products is their inherent physicochemical and biological instability. Important peptides such as insulin, calcitonin and cyclosporin A have been incorporated into LNFs. The association or encapsulation of peptides within lipid-based carriers has shown to protect the labile molecules against enzymatic degradation. This review describes strategies used for the formulation of peptides and some methods used for the assessment of association efficiency. The advantages and drawbacks of such carriers are also described.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Drug delivery, Lipids, Nanoformulations, Peptides
National Category
Other Chemistry Topics Physical Chemistry Pharmaceutical Sciences
Identifiers
urn:nbn:se:ri:diva-90 (URN)10.1016/j.ijpharm.2016.02.019 (DOI)2-s2.0-84959179307 (Scopus ID)
Available from: 2016-05-24 Created: 2016-04-28 Last updated: 2019-06-17Bibliographically approved
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4122-732x

Search in DiVA

Show all publications
v. 2.35.8