CR Competence AB

Lund, Sweden

CR Competence AB

Lund, Sweden
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Ristic T.,Tosama D.o.o. | Lasic S.,CR Competence AB | Kosalec I.,University of Zagreb | Bracic M.,Savatech D.o.o. | Fras-Zemljic L.,University of Maribor
Reactive and Functional Polymers | Year: 2015

Chitosan (CS) and trimethyl chitosan (TMC) solutions, as well as nanoparticles synthesized by ionic gelation method are studied. Their characterization is focused on determining the charge and antimicrobial properties against common pathogenic microorganisms and Lactobacillus spp., usually found in resident microbiota of vaginal and gastrointestinal tract. Special emphasis is given to the evaluation of antimicrobial activity in relation to the available cationic charge and the presence of nano-sized chitosan in comparison with chitosan macromolecules. In order to investigate the chitosan's antimicrobial mode of action diffusion nuclear magnetic resonance (D-NMR) is used as a novel approach. This technique enables the monitoring of chitosan nanoparticles (CSNP) effects onto healthy Lactobacillus cells. D-NMR results indicate that CSNP interact with the membrane of Lactobacillus cells, causing the perturbation of the membrane wall and lead to the death of the cells, suggesting the mechanism of Lactobacillus inhibition caused by CSNP. Lactobacillus inhibition is also reflected in low minimal inhibitory concentration (MIC). © 2015 Published by Elsevier B.V.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.77M | Year: 2014

The BIopolymer BAsed FOOd Delivery Systems (BIBAFOODS) network will train young researchers for the advancement of food science and technology, by providing them with the complementary skills necessary to develop the future sustainable food industry and entrepreneurial skills crucial for creating biotechnological food oriented start-up companies. This collaborative training network will combine the complementary training capabilities of each individual partner institution to improve the trainees chances for employment and promote health and welfare in the EC by providing the capability to develop novel functional foods. The scientific focus of the research training is on colloidal delivery systems to protect and deliver active components via foods, resulting in novel functional foods. The development of these systems is to be based on only food-grade ingredients and upon economical feasible processes. The hypothesis is that the materials and coatings can be made responsive to the external chemical conditions and therefore suitable for controlled releases targeted at a desired stage during food processing or at a specific point during digestion of the food, e.g. in the intestinal tract. This will involve probiotic bacteria and enzymes that are liberated and allowed to be active in a controllable way. The ultimate successful materials ensure stability of the active component during long term storage prior to food production, during food production or during digestion, but at the same time liberating the active component at the right point. The behaviour and interaction of the delivery systems will be studied by simulation of gastric and intestinal conditions and by implementation in food production and formulation into probiotic products. To summarize, through the training in BIBAFOODS, 14 young researchers will achieve superior qualifications that will make them highly competitive and attractive for the European food and bio-tech industry.


Knoos P.,Lund University | Svensson A.V.,Teknologisk Institute | Ulvenlund S.,CR Competence AB | Wahlgren M.,Lund University
PLoS ONE | Year: 2015

A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated. © 2015 Knöös et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | Lund University, CR Competence AB and Teknologisk Institute
Type: Journal Article | Journal: PloS one | Year: 2015

A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.


Yanez Arteta M.,Lund University | Ainalem M.-L.,European Spallation Source ESS AB | Porcar L.,Laue Langevin Institute | Martel A.,Laue Langevin Institute | And 7 more authors.
Journal of Physical Chemistry B | Year: 2014

We have investigated the interactions between cationic poly(amidoamine) (PAMAM) dendrimers of generation 4 (G4), a potential gene transfection vector, with net-anionic model biomembranes composed of different ratios of zwitterionic phosphocholine (PC) and anionic phospho-l-serine (PS) phospholipids. Two types of model membranes were used: solid-supported bilayers, prepared with lipids carrying palmitoyl-oleoyl (PO) and diphytanoyl (DPh) acyl chains, and free-standing bilayers, formed at the interface between two aqueous droplets in oil (droplet interface bilayers, DIBs) using the DPh-based lipids. G4 dendrimers were found to translocate through POPC:POPS bilayers deposited on silica surfaces. The charge density of the bilayer affects translocation, which is reduced when the ionic strength increases. This shows that the dendrimer-bilayer interactions are largely controlled by their electrostatic attraction. The structure of the solid-supported bilayers remains intact upon translocation of the dendrimer. However, the amount of lipids in the bilayer decreases and dendrimer/lipid aggregates are formed in bulk solution, which can be deposited on the interfacial layers upon dilution of the system with dendrimer-free solvent. Electrophysiology measurements on DIBs confirm that G4 dendrimers cross the lipid membranes containing PS, which then become more permeable to ions. The obtained results have implications for PAMAM dendrimers as delivery vehicles to cells. (Figure Presented). © 2014 American Chemical Society.


Knoos P.,Lund University | Wahlgren M.,Lund University | Topgaard D.,Lund University | Ulvenlund S.,CR Competence AB | Piculell L.,Lund University
Journal of Physical Chemistry B | Year: 2014

A combination of NMR chemical shift imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when tablets of hydrophobically modified poly(acrylic acid) loaded with a drug (griseofulvin) swell in water in the presence or absence of surfactant (sodium octylbenzenesulfonate). The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective surfactant transport that occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Because of the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outward as the matrix swells. The added surfactant has little effect on the transport of drug because both undissolved solid drug and surfactant-solubilized drug function as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix. © 2014 American Chemical Society.


Ulvenlund S.,CR Competence AB | Topgaard D.,Lund University | Sparr E.,Lund University | Gustavsson S.,Lund University
Advanced Materials - TechConnect Briefs 2016 | Year: 2016

Solid-state and diffusion NMR spectroscopy are versatile tools that allow for studies of both structure and dynamics of complex solid and semisolid materials. We have developed a suit of pulse sequences based on polarization transfer that is readily applied to studies of formulations and their interactions with biological systems. In the present paper, we illustrate its applicability by using an incompletely hydrated surfactant system (tetradecyl-maltoside, C14G2) and skin (stratum corneum, SC) as examples. In the former case, solid-state NMR has allowed us to study the dynamics of the system at the level of individual functional groups, and also to derive the surprisingly complex C14G2-H2O phase diagram at water contents <5%. For SC, NMR data has allowed us to study the effect of natural moisturizing factor (NMF) on the dynamics of its lipid and protein constituents. The results challenge the conventional view that NMF protects the skin from dryness by increasing its water content.


Knoos P.,Lund University | Topgaard D.,Lund University | Wahlgren M.,Lund University | Ulvenlund S.,Lund University | And 2 more authors.
Langmuir | Year: 2013

A new technique has been developed using NMR chemical shift imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly(acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release, and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent. © 2013 American Chemical Society.


PubMed | Lund University, CR Competence AB and University of Campinas
Type: | Journal: Colloids and surfaces. B, Biointerfaces | Year: 2016

Lipases are key components in the mechanisms underlying the persistence and virulence of infections by fungi, and thus also promising triggers for bioresponsive lipid-based liquid crystalline nanoparticles. We here propose a platform in which only a minor component of the formulation is susceptible to cleavage by lipase and where hydrolysis triggers a controlled phase transition within the nanoparticles that can potentially allow for an extended drug release. The responsive formulations were composed of phytantriol, which was included as a non-cleavable major component and polysorbate 80, which serves both as nanoparticle stabilizer and potential lipase target. To monitor the structural changes resulting from lipase activity with sufficient time resolution, we used synchrotron small angle x-ray scattering. Comparing the effect of the two different lipases used in this work, lipase B from Candida Antarctica, (CALB) and lipase from Rhizomucor miehei (RMML), only CALB induced phase transition from bicontinuous reverse cubic to reverse hexagonal phase within the particles. This phase transition can be attributed to an increasing amount of oleic acid formed on cleavage of the polysorbate 80. However, when also a small amount of a cationic surfactant was included in the formulation, RMML could trigger the corresponding phase transition as well. The difference in activity between the two lipases can tentatively be explained by a difference in their interaction with the nanoparticle surface. Thus, a bioresponsive system for treating fungal infections, with a tunable selectivity for different types of lipases, could be obtained by tuning the composition of the nanoparticle formulation.


Ivanov A.E.,Malmö University | Halthur T.,CR Competence AB | Ljunggren L.,Malmö University
Journal of Environmental Chemical Engineering | Year: 2016

Monolithic composites of Polyphepan® or Kraft lignin embedded in a poly(vinyl alcohol) (PVA) matrix were synthesized using cryogelation technique and studied as flow permeable adsorbents for bisphenol A and erythromycin removal from water. Adsorption isotherms of bisphenol A on pristine Polyphepan provided the equilibrium dissociation constant KL = 2.6 × 10-6 M and the maximal binding capacity Qmax = 20 μmol/g; for erythromycin KL was in the 9.6 × 10-6 M to 5.8 × 10-5 M range, and Qmax was between 55 μmol/g and 94 μmol/g. Embedment of lignins into PVA cryogels resulted in monoliths with adequate flow permeability and the composites essentially retained the binding capacity for both bisphenol A and erythromycin. Percolation of contaminated water through the monoliths resulted in 10-fold reduction of the pollutant concentrations within 12-70 column volumes of the effluent. Due to the higher loading of lignin, the Kraft lignin-PVA composite showed higher adsorption capacity for erythromycin than Polyphepan-PVA. Stability and reversible compression of the monoliths in the flow of water were studied. Limitations are associated with leakage of soluble lignin, strongly expressed in the case of Kraft lignin-containing composites. © 2016 Elsevier Ltd. All rights reserved.

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