Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Sabina P. Strand is active.

Publication


Featured researches published by Sabina P. Strand.


Biomaterials | 2010

Molecular design of chitosan gene delivery systems with an optimized balance between polyplex stability and polyplex unpacking

Sabina P. Strand; Sylvie Lélu; Nina Kristine Reitan; Catharina de Lange Davies; Per Artursson; Kjell M. Vårum

Chitosan is an attractive gene delivery vehicle, but the criteria and strategies for the design of efficient chitosan gene delivery systems remain unclear. The purpose of this work was to investigate how the strength of the charge-based interaction between chitosan and DNA determines the gene expression levels and to design chitosan vectors with an optimized balance between polyplex stability and polyplex unpacking. Using 21 formulations based on low molecular weight chitosans with constant charge density and a number-average degree of polymerization (DPn) in the range of 21-88 (M(w) 4.7-33kDa), we studied the relationship between the chain length and the formulation properties, cellular uptake of polyplexes and gene transfer efficacy. We were able to identify a narrow interval of DPn31-42 that mediated the maximum level of transgene expression. An increase in chain length and/or the amino-phosphate (A/P) ratio reduced and delayed transgene expression. Compared to DPn31, transfection with the same amount of DPn72 or DPn88 resulted in 10-fold-lower expression levels. The gene transfer pattern correlated with the ability of heparin to release DNA from the polyplexes. As a tool to facilitate the unpacking of the polyplexes, we substituted the chitosans with uncharged oligosaccharides that reduced the interaction with DNA. The substitution of chitosans that originally yielded too stable polyplexes, such as DPn72 and DPn88 resulted in a 5-10-fold enhancement of the expression levels. However, the substitution of chitosans shorter than DP28 completely abolished transfection. Tailoring of the chain length and the substitution of chitosan were shown to be feasible tools to modulate the electrostatic interactions between the chitosan and DNA and to design chitosans with an optimized balance between polyplex stability and polyplex unpacking.


Colloids and Surfaces B: Biointerfaces | 2003

Interactions between chitosans and bacterial suspensions : adsorption and flocculation

Sabina P. Strand; Kjell M. Vårum; Kjetill Østgaard

Abstract Chitosans with different chemical composition were applied to flocculate Escherichia coli suspensions. The adsorption of chitosans was followed both by applying fluorescence labeled chitosans and monitoring changes in zeta potential values of the bacterial cells. The effects of chitosan molecular weight and composition, identified by the fraction of acetylated units ( F A ), were examined, as well as environmental conditions such as pH and ionic strength. The adsorption of chitosans to E. coli cells increased strongly with pH, the adsorbed amounts increased approximately 40% if pH was increased from pH 5 to 6.5. Despite their low charge density, the chitosans with higher F A adsorbed in higher amounts and reversed the cell surface charge most effectively. The chitosans with low molecular weights adsorbed most. Ionic strength did not affect the adsorption of highly acetylated chitosan with F A 0.49, whereas for chitosan with F A 0.01, adsorption increased with ionic strength. The combination of flocculation and adsorption data clearly showed that charge neutralization was not the main flocculation mechanism. Several results pointed to bridging as one dominating mechanism for flocculation.


Journal of Controlled Release | 2012

siRNA delivery with chitosan nanoparticles: Molecular properties favoring efficient gene silencing

Jostein Malmo; Hanne Sørgård; Kjell M. Vårum; Sabina P. Strand

Chitosan has gained increasing interest for siRNA delivery. Although chitosan covers a family of structurally different polysaccharides, most siRNA delivery studies have been performed with conventional partially N-acetylated chitosans. Herein, the purpose was to identify fundamental chitosan molecular properties favoring siRNA delivery and efficient gene silencing in mammalian cells. Nanoparticles were prepared from well-defined chitosans of various chemical compositions, degrees of polymerization (DP(n)) and chain architectures. Structure-activity relationships were determined by the cellular uptake of siRNA and the knockdown efficiency at mRNA and protein levels. Additionally, the nanoparticle cytotoxicity was evaluated on the basis of cellular metabolic activity and membrane integrity. Our results show that the most efficient gene silencing was achieved using fully de-N-acetylated chitosans with intermediate chain lengths (DP(n) 100-300). These chitosans mediated efficient siRNA delivery at low siRNA concentrations and, in several cell lines, potent long-term silencing of both exogenous and endogenous target genes, with minimal cytotoxicity.


International Journal of Food Microbiology | 2011

Antibacterial activity of chemically defined chitosans: Influence of molecular weight, degree of acetylation and test organism

Hilde Mellegård; Sabina P. Strand; Bjørn E. Christensen; Per Einar Granum; Simon P Hardy

Chitosans, polysaccharides obtained from the exoskeleton of crustaceans, have been shown to exert antibacterial activity in vitro and their use as a food preservative is of growing interest. However, beyond a consensus that chitosan appears to disrupt the bacterial cell membrane, published data are inconsistent on the chemical characteristics that confer the antibacterial activity of chitosan. While most authors agree that the net charge density of the polymer (reflected in the fraction of positively charged amino groups at the C-2 position of the glucosamine unit) is an important factor in antibacterial activity, conflicting data have been reported on the effect of molecular weight and on the susceptibility among different bacterial species to chitosan. Therefore, we prepared batches of water-soluble hydrochloride salts of chitosans with weight average molecular weights (M(w)) of 2-224kDa and degree of acetylation of 0.16 and 0.48. Their antibacterial activity was evaluated using tube inhibition assays and membrane integrity assays (N-Phenyl-1-naphthylamine fluorescence and potassium release) against Bacillus cereus, Escherichia coli, Salmonella Typhimurium and three lipopolysaccharide mutants of E. coli and S. Typhimurium. Chitosans with lower degree of acetylation (F(A)=0.16) were more active than the more acetylated chitosans (F(A)=0.48). No trends in antibacterial action related to increasing or decreasing M(w) were observed although one of the chitosans (M(w) 28.4kDa, F(A)=0.16) was more active than the other chitosans, inhibiting growth and permeabilizing the membrane of all the test strains included. The test strains varied in their susceptibility to the different chitosans with wild type S. Typhimurium more resistant than the wild type E. coli. Salmonellae lipopolysaccharide mutants were more susceptible than the matched wild type strain. Our results show that the chitosan preparation details are critically important in identifying the antibacterial features that target different test organisms.


Water Research | 2002

Efficiency of chitosans applied for flocculation of different bacteria.

Sabina P. Strand; Thomas Nordengen; Kjetill Østgaard

Three types of well-characterized chitosans of different composition were applied to flocculate 8 different bacterial species. The aim of this study was to relate chitosan structure and flocculation characteristic to general bacterial characteristics such as the cell surface charge and hydrophobicity. Large differences in the flocculation efficiency of chitosan were found between different bacterial suspensions, both regarding the effective chitosan concentrations and the optimal type of chitosan. However, no correlation was observed between general surface characteristics of bacteria and flocculation by chitosan of different composition. It may be concluded that purely electrostatic interactions did not play a dominant role in flocculation of Gram-negative bacteria in this study. The presence of GlcNAc residues had clearly beneficial effects on flocculation in such cases.


Biomacromolecules | 2008

Tailoring of Chitosans for Gene Delivery: Novel Self-Branched Glycosylated Chitosan Oligomers with Improved Functional Properties

Sabina P. Strand; Mohamed M. Issa; Bjørn E. Christensen; Kjell M. Vårum; Per Artursson

Chitosan is a promising biomaterial with an attractive safety profile; however, its application potential for gene delivery is hampered by poor compatibility at physiological pH values. Here we have tailored the molecular architecture of chitosan to improve the functional properties and gene transfer efficacy of chitosan oligomers and have developed self-branched glycosylated chitosan oligomer (SB-TCO) substituted with a trisaccharide containing N-acetylglucosamine, AAM. SB-TCO was prepared by controlled depolymerization of chitosan, followed by simultaneous branching and AAM substitution. The product was fully soluble at physiological pH and complexed plasmid DNA into polyplexes of high colloidal and physical stability. SB-TCO displayed high transfection efficacy in HEK293 cells, reaching transfection efficiencies of up to 70%, and large amounts of transgene were produced. Gene transfer efficacy was confirmed in HepG2 cells, where gene expression levels mediated by SB-TCO were up to 10 and 4 times higher than those obtained with unsubstituted and substituted linear oligomers, respectively. The rapid onset of transgene expression in both cell lines indicates efficient DNA release and transcription from SB-TCO polyplexes. In comparison with 22 kDa linear PEI-based transfection reagent used as the control, SB-TCO possessed higher gene transfer efficacy, significantly lower cytotoxicity, and improved serum compatibility.


Biomacromolecules | 2011

Effect of Chitosan Chain Architecture on Gene Delivery: Comparison of Self-Branched and Linear Chitosans

Jostein Malmo; Kjell M. Vårum; Sabina P. Strand

Chitosan possesses many characteristics of an ideal gene delivery system. However, the transfection efficiency of conventional chitosans is generally found to be low. In this study, we investigated the self-branching of chitosans as a strategy to improve its gene transfer properties without compromising its safety profile. Self-branched (SB) and self-branched trisaccharide-substituted (SBTCO) chitosans with molecular weights of 11-71 kDa were synthesized, characterized, and compared with their linear counterparts with respect to transfection efficiency, cellular uptake, formulation stability, and cytotoxicity. Our studies show that in contrast with unmodified linear chitosans that were unable to transfect HeLa cells, self-branched chitosans mediated high transfection efficiencies. The most efficient chitosan, SBTCO30, yielded gene expression levels two and five times higher than those of Lipofectamine and Exgen, respectively, and was nontoxic to cells. Nanoparticles formed with SBTCO chitosans exhibited a higher colloidal stability of formulation, efficient internalization without excessive cell surface binding, and low cytotoxicity.


IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control | 2013

Mechanisms of the ultrasound-mediated intracellular delivery of liposomes and dextrans

Mercy Afadzi; Sabina P. Strand; Esben A. Nilssen; S-E Masoy; Tonni Franke Johansen; Rune Hansen; Bjørn Angelsen; C de Lange Davies

The mechanism involved in the ultrasound-enhanced intracellular delivery of fluorescein-isothiocyanate (FITC)-dextran (molecular weight 4 to 2000 kDa) and liposomes containing doxorubicin (Dox) was studied using HeLa cells and an ultrasound transducer at 300 kHz, varying the acoustic power. The cellular uptake and cell viability were measured using flow cytometry and confocal microscopy. The role of endocytosis was investigated by inhibiting clathrin- and caveolae-mediated endocytosis, as well as macropinocytosis. Microbubbles were found to be required during ultrasound treatment to obtain enhanced cellular uptake. The percentage of cells internalizing Dox and dextran increased with increasing mechanical index. Confocal images and flow cytometric analysis indicated that the liposomes were disrupted extracellularly and that released Dox was taken up by the cells. The percentage of cells internalizing dextran was independent of the molecular weight of dextrans, but the amount of the small 4-kDa dextran molecules internalized per cell was higher than for the other dextrans. The inhibition of endocytosis during ultrasound exposure resulted in a significant decrease in cellular uptake of dextrans. Therefore, the improved uptake of Dox and dextrans may be a result of both sonoporation and endocytosis.


PLOS ONE | 2013

Nanoparticle Mediated P-Glycoprotein Silencing for Improved Drug Delivery across the Blood-Brain Barrier: A siRNA-Chitosan Approach

Jostein Malmo; Axel Sandvig; Kjell M. Vårum; Sabina P. Strand

The blood-brain barrier (BBB), composed of tightly organized endothelial cells, limits the availability of drugs to therapeutic targets in the central nervous system. The barrier is maintained by membrane bound efflux pumps efficiently transporting specific xenobiotics back into the blood. The efflux pump P-glycoprotein (P-gp), expressed at high levels in brain endothelial cells, has several drug substrates. Consequently, siRNA mediated silencing of the P-gp gene is one possible strategy how to improve the delivery of drugs to the brain. Herein, we investigated the potential of siRNA-chitosan nanoparticles in silencing P-gp in a BBB model. We show that the transfection of rat brain endothelial cells mediated effective knockdown of P-gp with subsequent decrease in P-gp substrate efflux. This resulted in increased cellular delivery and efficacy of the model drug doxorubicin.


International Journal of Biological Macromolecules | 2012

Cellular uptake of DNA-chitosan nanoparticles: the role of clathrin- and caveolae-mediated pathways.

Zuzana Garaiova; Sabina P. Strand; Nina Kristine Reitan; Sylvie Lélu; Sigmund Ø. Størset; Kristian Berg; Jostein Malmo; Oladayo Folasire; Astrid Bjørkøy; Catharina de Lange Davies

The success of gene therapy depends on efficient delivery of DNA and requires a vector. A promising non-viral vector is chitosan. We tailored chitosan to optimize it for transfection by synthesizing self-branched and trisaccharide-substituted chitosan oligomers (SBTCO), which show superior transfection efficacy compared with linear chitosan (LCO). The aim of the work was to compare the cellular uptake and endocytic pathways of polyplexes formed by LCO and SBTCO. Both polyplexes were taken up by the majority of the cells, but the uptake of LCO was lower than SBTCO polyplexes. LCO polyplexes were internalized through both clathrin-dependent and clathrin-independent pathways, whereas SBTCO polyplexes were primarily taken up by clathrin-independent endocytosis. The different level of cellular uptake and the distinct endocytic pathways, may explain the difference in transfection efficacy. This was supported by the observation that photochemical internalization increased the transfection by LCO polyplexes considerably, whereas no effect on transfection was found for SBTCO polyplexes.

Collaboration


Dive into the Sabina P. Strand's collaboration.

Top Co-Authors

Avatar

Kjell M. Vårum

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Bjørn E. Christensen

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Catharina de Lange Davies

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Nina Kristine Reitan

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Jostein Malmo

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Kjetill Østgaard

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Kristoffer Tømmeraas

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Sylvie Lélu

Norwegian University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Astrid Bjørkøy

Norwegian University of Science and Technology

View shared research outputs
Researchain Logo
Decentralizing Knowledge