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Träfflista för sökning "AMNE:(MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper) ;pers:(Hansson Per)"

Sökning: AMNE:(MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmaceutiska vetenskaper) > Hansson Per

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1.
  • Bysell, Helena, et al. (författare)
  • Effect of hydrophobicity on the interaction between antimicrobial peptides and poly(acrylic acid) microgels
  • 2010
  • Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:3, s. 1307-1313
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of peptide hydrophobicity on the interaction between antimicrobial peptides and poly(acrylic, acid) microgels wits studied by end-tagging the kininogen-derived antimicrobial peptide GKHKNKGKKNGKHNGWK (GKH17) and its truncated variant KNKGKKNGKH (KNK10) with oligotryptophan groups of different lengths. Microgel deswelling and reswelling in response to peptide binding and release was studied by micromanipulator-assisted light- and fluorescence microscopy, peptide uptake in microgels was determined from solution depletion measurements, and peptide oligomerization was monitored by fluorescence spectroscopy. Results showed that oligomerizition/aggregation of the hydrophobically end-tagged peptides is either absent or characterized by exposure of the tryptophan residues to the aqueous ambient, the latter suggesting small aggregation numbers. In addition, peptide uptake and affinity to the poly(acrylic acid) microgels increase with the number of trypthophan residues in the hydrophobic end tag, whereas peptide-induced microgel deswelling kinetics did not display this tag-length dependence to the same extent. Instead, long end tags resulted in anomalous shell formation, opposing further peptide-induced network deswelling. Theoretical modeling suggested that the deswelling kinetics in response to peptide binding is largely controlled by stagnant layer diffusion, but also that for peptides with Sufficiently long hydrophobic tags, the shell constitutes an additional diffusion barrier, thus resulting in slower microgel deswelling. In addition, GKH17 and KNK10 peptides lacking the tryptophan end tags were Substantially released on reducing peptide-microgel electrostatic interactions through addition of salt, an effect more pronounced for the shorter KNK10 peptide, whereas the hydrophobically end-tagged peptides remained bound to the microgels also at high ionic strength.
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2.
  • Wanselius, Marcus, et al. (författare)
  • Microfluidics platform for studies of peptide - polyelectrolyte interaction
  • 2022
  • Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 621
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcutaneous injection is one of the most common approaches for administering biopharmaceuticals unsuitable for oral delivery. However, there is a lack of methods to predict the behavior of biopharmaceuticals within the extracellular matrix of the subcutaneous tissue. In this work, we present a novel miniaturized microfluidic-based in vitro method able to investigate interactions between drug molecules and the polymers of the subcutaneous extracellular matrix. To validate the method, microgels consisting of, respectively, covalently cross-linked hy-aluronic acid, polyacrylic acid, and commercially available DC BeadTM, were exposed to three model substances: cytochrome C, protamine sulfate and amitriptyline hydrochloride. These components were chosen to include systems with widely different physiochemical properties (charge, size, self-assembly, etc.) The experimental results were compared with theoretical predictions from a gel model developed earlier. The results show that the method is suitable as a rapid screening method for automated, large-scale, probing of interactions between biopolymers and drug molecules, with small consumption of material.
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3.
  • Månsson, Ronja, et al. (författare)
  • Effects of Peptide Secondary Structure on the Interaction with Oppositely Charged Microgels
  • 2011
  • Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 12:2, s. 419-424
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of peptide secondary structure on the interaction between antimicrobial peptides and oppositely charged poly(acrylic acid-co-acrylamide) microgels of various charge density was investigated for EFKRIVQRIKDFLRNLV (EFK17). Through D-enantiomer (EFK17-d/a; E(dF)KR(dI)VQR(dI)KD(dF)LRNLV) or tryptophan (EFK17-W/a; EWKRWVQRWKDFLRNLV) substitutions, both conformation-dependent and -independent amphiphilicity of this peptide could be precisely controlled. Peptide secondary structure was investigated by circular dichroism, whereas microgel deswelling and reswelling in response to peptide binding and release were studied by micromanipulator-assisted light and fluorescence microscopy, and peptide uptake in the microgels was determined from solution depletion measurements. Results show that peptide binding to the microgel is highly influenced by peptide secondary structure. EFK17-a, characterized by an idealized helix with all polar/charged amino acids located at one side of the helix, and all nonpolar/hydrophobic residues on the other, displays pronounced alpha-helix induction on peptide binding to the microgels. EFK17-d/a, on the other hand, displays no such amphiphilic helix induction. Mirroring this, EFK17-a displays substantially higher binding to the microgels than EFK17-d/a as well as much larger peptide-induced microgel deswelling. For EFK17-W/a, both conformation-dependent and -independent amphiphilicity effects were demonstrated. Overall, the results show that peptide conformational aspects need to be considered in peptide/microgel interactions, for example, in the design of microgel carrier systems for peptide drugs.
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4.
  • Nilsson, Peter, et al. (författare)
  • Effect of salt and surfactant concentration on the structure of polyacrylate gel/sutrfactant complexes
  • 2007
  • Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 111:37, s. 10959-10964
  • Tidskriftsartikel (refereegranskat)abstract
    • Small-angle X-ray scattering was used to elucidate the structure of crosslinked polyacrylate gel/ dodecyltrimethylammonium bromide complexes equilibrated in solutions of varying concentrations of surfactant and sodium bromide (NaBr). Samples were swollen with no ordering (micelle free), or they were collapsed with either several distinct peaks (cubic Pm3n) or one broad correlation peak (disordered micellar). The main factor determining the structure of the collapsed complexes was found to be the NaBr concentration, with the cubic structure existing up to similar to 150 mM NaBr and above which only the disordered micellar structure was found. Increasing the salt concentration decreases the polyion mediated attractive forces holding the micelles together causing swelling of the gel. At sufficiently high salt concentration the micelle-micelle distance in the gel becomes too large for the cubic structure to be retained, and it melts into a disordered micellar structure. As most samples were above the critical micelle concentration, the bulk of the surfactant was in the form of miscelles in the solution and the surfactant concentration thereby had only a minor influence on the structure. However, in the region around 150 mM Nal3r, increasing the surfactant concentration, at constant NaBr concentration, was found to change the structure from disordered micellar to ordered cubic and back to disordered again.
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5.
  • Widenbring, Ronja, 1985- (författare)
  • Microgel Interactions with Peptides and Proteins : Consequence of Peptide and Microgel Properties
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Microgels are lightly cross-linked hydrogel particles in the sub-micrometer to micrometer size range with a capacity to drastically change their volume in response to changes in the external environment. Microgels have an ability to bind and store substances such as biomacromolecular drugs, notably proteins and peptides, and release them upon stimuli, making them potential candidates as drug delivery vehicles and functional biomaterials. This thesis aims at clarifying important factors affecting peptide-microgel interactions. These interactions were studied by micromanipulator-assisted light and fluorescence microscopy focusing on microgel deswelling in response to peptide binding, as well as re-swelling in response to peptide release or enzymatic degradation. To evaluate peptide uptake in microgels, solution depletion measurements were used whereas the peptide secondary structure was investigated by circular dichroism. In addition, the peptide and enzyme distribution within microgels was analyzed with confocal microscopy.Results presented in this thesis demonstrate that peptide incorporation into microgels, as well as peptide-induced microgel deswelling, increases with peptide length and charge density. In addition, results demonstrate that the peptide charge (length) rather than peptide charge density determines microgels deswelling. End-to-end cyclization is shown to not noticeably influence peptide-microgel interactions, suggesting that peptide cyclization can be used in combination with oppositely charged microgel carriers to improve the proteolytic and chemical stability of the peptide compared to the corresponding linear variant. Peptide secondary structure is found to drastically affect peptide incorporation into, and release from, oppositely charged microgels. Furthermore, it is shown that microgel charge density, peptide molecular weight, and enzyme concentration all greatly influence microgel bound peptide degradation. Of importance for applications, protective effects of microgels against proteolytic peptide degradation are observed only at sufficiently high microgel charge densities. Enzyme-mediated microgel degradation is shown to increase with increasing enzyme concentration, while an increased peptide loading in microgels causes a concentration-dependent decrease in microgel degradation.Taken together, results obtained in this work have provided some insight into factors of importance for rational use of microgels as delivery systems for protein or peptide drugs, but also in a host of other biomedical applications using weakly cross-linked polymer systems.
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6.
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7.
  • Ahnfelt, Emelie, et al. (författare)
  • In Vitro Release Mechanisms of Doxorubicin From a Clinical Bead Drug-Delivery System
  • 2016
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 105:11, s. 3387-3398
  • Tidskriftsartikel (refereegranskat)abstract
    • The release rate of doxorubicin (DOX) from the drug-delivery system (DDS), DC Bead, was studied by 2 miniaturized in vitro methods: free-flowing and sample reservoir. The dependencies of the release mechanisms on in vitro system conditions were investigated experimentally and by theoretical modeling. An inverse relationship was found between release rates and bead size, most likely due to the greater total surface area. The release rates correlated positively with temperature, release medium volume, and buffer strength, although the release medium volume had larger effect than the buffer strength. The sample reservoir method generated slower release rates, which described the in vivo release profile more accurately than the free-flowing method. There was no difference between a pH of 6.3 or 7.4 on the release rate, implying that the slightly acidic tumor microenvironment is less importance for drug release. A positive correlation between stirring rate and release rate for all DDS sizes was observed, which suggests film controlled release. Theoretical modeling highlighted the influence of local equilibrium of protonation, self-aggregation, and bead material interactions of DOX. The theoretical release model might describe the observed larger sensitivity of the release rate to the volume of the release medium compared to buffer strength. A combination of miniaturized in vitro methods and theoretical modeling are useful to identify the important parameters and processes for DOX release from a micro gel-based DDS.
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8.
  • Ahnfelt, Emelie, et al. (författare)
  • Single bead investigation of a clinical drug delivery system – a novel release mechanism
  • 2018
  • Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 292, s. 235-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Microgels, such as polymeric hydrogels, are currently used as drug delivery devices (DDSs) for chemotherapeutics and/or unstable drugs. The clinical DDS DC bead® was studied with respect to loading and release, measured as relative bead-volume, of six amphiphilic molecules in a micropipette-assisted microscopy method. Theoretical models for loading and release was used to increase the mechanistic understanding of the DDS.It was shown that equilibrium loading was independent of amphiphile concentration. The loading model showed that the rate-determining step was diffusion of the molecule from the bulk to the bead surface (‘film control’). Calculations with the developed and applied release model on the release kinetics were consistent with the observations, as the amphiphiles distribute unevenly in the bead. The rate determining step of the release was the diffusion of the amphiphile molecule through the developed amphiphile-free depletion layer. The release rate is determined by the diffusivity and the tendency for aggregation of the amphiphile where a weak tendency for aggregation (i.e. a large cacb) lead to faster release. Salt was necessary for the release to happen, but at physiological concentrations the entry of salt was not rate-determining. This study provides valuable insights into the loading to and release from the DDS. Also, a novel release mechanism of the clinically used DDS is suggested.
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9.
  • Al-Tikriti, Yassir, et al. (författare)
  • A small-angle X-ray scattering study of amphiphilic drug self-assemblies in polyacrylate microgels
  • 2024
  • Ingår i: Colloids and Surfaces A. - : Elsevier. - 0927-7757 .- 1873-4359. ; 686
  • Tidskriftsartikel (refereegranskat)abstract
    • Common ionisable amphiphilic drug molecules form micelles in aqueous solution. Loaded onto oppositely charged polyelectrolyte microgels they associate with the network chains to form dense complex phases. The self-assembling properties control the loading and release properties in drug delivery applications of microgel systems but little is known about the nature of the aggregates and the phase structure. In this paper, we investigated the size and organization of the self-assemblies formed by the hydrochloride salts of amitriptyline (AMT), chlorpromazine (CPZ), and doxepin (DXP) in sodium polyacrylate microgels. Small-angle X-ray scattering (SAXS) was used to determine the microstructure of drug loaded microgels in aqueous environment at ionic strengths relevant for drug loading (0.01 M) and release (0.15 M). The composition of drug loaded microgels was determined by means of a purpose built microscopy cell and UV spectroscopy measurements. Upon drug loading the microgels formed complex phases of low water content. SAXS experiments showed that the drugs formed oblate shaped or spherical micelles displaying local ordering but without long-range ordering even at very high micelle volume fractions. The local ordering resembled the packing of randomly packed hard oblates and spheres. The aggregation number of AMT varied between 10 and 49 depending on the composition. Incorporation of the uncharged base form of the drug caused a transformation of oblate shaped (aspect ratio ∼ 0.4) to spherical micelles, accompanied by an abrupt increase of the aggregation number. Variation of the ionic strength had minor effects on the aggregation number. CPZ formed oblate shape micelles (aspect ratios 0.3–0.4) with aggregation number between 9 and 30. DXP formed oblate shape micelles (aspect ratios 0.3–0.4) with aggregation numbers 10 − 11 at all studied compositions. The results provide a structural basis for, and justification of, previously assumed microstructures underlying mechanistic models of drug-microgel interactions and drug release.
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10.
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