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  • 1. Dahlberg, C
    et al.
    Millqvist-Fureby, A
    YKI – Ytkemiska institutet.
    Schuleit, M
    Dvinskikh, SV
    Furó, I
    Polymer mobilization and drug release during tablet swelling. A 1H NMR and NMR microimaging study2007In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 122, p. 199-205Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to investigate the swelling characteristics of a hydroxypropyl methylcellulose (HPMC) matrix incorporating the hydrophilic drug antipyrine. We have used this matrix to introduce a novel analytical method, which allows us to obtain within one experimental setup information about the molecular processes of the polymer carrier and its impact on drug release. Nuclear magnetic resonance (NMR) imaging revealed in situ the swelling behavior of tablets when exposed to water. By using deuterated water, the spatial distribution and molecular dynamics of HPMC and their kinetics during swelling could be observed selectively. In parallel, NMR spectroscopy provided the concentration of the drug released into the aqueous phase. We find that both swelling and release are diffusion controlled. The ability of monitoring those two processes using the same experimental setup enables mapping their interconnection, which points on the importance and potential of this analytical technique for further application in other drug delivery forms.

  • 2.
    Häbel, Hennrike
    et al.
    Chalmers University of Technology, Sweden; University of Gothenburg, Sweden.
    Andersson, Helene
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Food and Bioscience. Chalmers University of Technology, Sweden.
    Olsson, Anna
    Chalmers University of Technology, Sweden.
    Olsson, Eva
    Chalmers University of Technology, Sweden.
    Larsson, Anette
    Chalmers University of Technology, Sweden.
    Särkkä, Aila
    Chalmers University of Technology, Sweden; University of Gothenburg, Sweden.
    Characterization of pore structure of polymer blended films used for controlled drug release2016In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 222, p. 151-158Article in journal (Refereed)
    Abstract [en]

    The characterization of the pore structure in pharmaceutical coatings is crucial for understanding and controlling mass transport properties and function in controlled drug release. Since the drug release rate can be associated with the film permeability, the effect of the pore structure on the permeability is important to study. In this paper, a new approach for characterizing the pore structure in polymer blended films was developed based on an image processing procedure for given two-dimensional scanning electron microscopy images of film cross-sections. The focus was on different measures for characterizing the complexity of the shape of a pore. The pore characterization developed was applied to ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) blended films, often used as pharmaceutical coatings, where HPC acts as the pore former. It was studied how two different HPC viscosity grades influence the pore structure and, hence, mass transport through the respective films. The film with higher HPC viscosity grade had been observed to be more permeable than the other in a previous study; however, experiments had failed to show a difference between their pore structures. By instead characterizing the pore structures using tools from image analysis, statistically significant differences in pore area fraction and pore shape were identified. More specifically, it was found that the more permeable film with higher HPC viscosity grade seemed to have more extended and complex pore shapes than the film with lower HPC viscosity grade. This result indicates a greater degree of connectivity in the film with higher permeability and statistically confirms hypotheses on permeability from related experimental studies.

  • 3.
    Rozenbaum, Rene
    et al.
    University of Groningen, Netherlands.
    Su, Linzhu
    University of Groningen, Netherlands; Nankai University, China.
    Umerska, Anita
    Université Bretagne, France.
    Eveillard, Matthiou
    Université de Nantes, France.
    Håkansson, Joakim
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Mahlapuu, Margit
    Promore Pharma, Sweden.
    Huang, Fan
    Peking Union Medical College, China.
    Liu, Jian feng
    Peking Union Medical College, China.
    Zhang, Zhenkun
    Nankai University, China.
    Shi, Linqi
    Nankai University, China.
    van der Mei, Henny
    University of Groningen, Netherlands.
    Busscher, Henk
    University of Groningen, Netherlands.
    Sharma, Prashant
    University of Groningen, Netherlands.
    Antimicrobial synergy of monolaurin lipid nanocapsules with adsorbed antimicrobial peptides against Staphylococcus aureus biofilms in vitro is absent in vivo2019In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 293, p. 73-83Article in journal (Refereed)
    Abstract [en]

    Bacterial infections are mostly due to bacteria in their biofilm-mode of growth, while penetrability of antimicrobials into infectious biofilms and increasing antibiotic resistance hamper infection treatment. In-vitro, monolaurin lipid nanocapsules (ML-LNCs) carrying adsorbed antimicrobial peptides (AMPs) displayed synergistic efficacy against planktonic Staphylococcus aureus, but it has not been demonstrated, neither in-vitro nor in-vivo, that such ML-LNCs penetrate into infectious S. aureus biofilms and maintain synergy with AMPs. This study investigates the release mechanism of AMPs from ML-LNCs and possible antimicrobial synergy of ML-LNCs with the AMPs DPK-060 and LL-37 against S. aureus biofilms in-vitro and in a therapeutic, murine, infected wound-healing model. Zeta potentials demonstrated that AMP release from ML-LNCs was controlled by the AMP concentration in suspension. Both AMPs demonstrated no antimicrobial efficacy against four staphylococcal strains in a planktonic mode, while a checkerboard assay showed synergistic antimicrobial efficacy when ML-LNCs and DPK-060 were combined, but not for combinations of ML-LNCs and LL-37. Similar effects were seen for growth reduction of staphylococcal biofilms, with antimicrobial synergy persisting only for ML-LNCs at the highest level of DPK-060 or LL-37 adsorption. Healing of wounds infected with bioluminescent S. aureus Xen36, treated with ML-LNCs alone, was faster when treated with PBS, while AMPs alone did not yield faster wound-healing than PBS. Faster, synergistic wound-healing due to ML-LNCs with adsorbed DPK-060, was absent in-vivo. Summarizing, antimicrobial synergy of ML-LNCs with adsorbed antimicrobial peptides as seen in-vitro, is absent in in-vivo healing of infected wounds, likely because host AMPs adapted the synergistic role of the AMPs added. Thus, conclusions regarding synergistic antimicrobial efficacy, should not be drawn from planktonic data, while even in-vitro biofilm data bear little relevance for the in-vivo situation. © 2018

  • 4.
    Svagan, Anna J.
    et al.
    KTH Royal Institute of Technology, Sweden; University of Copenhagen, Denmark.
    Benjamins, Jan-Willem
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Al-Ansari, Zeinab
    University of Copenhagen, Denmark.
    Shalom, Daniel Bar
    University of Copenhagen, Denmark.
    Müllertz, Anette
    University of Copenhagen, Denmark.
    Wågberg, Lars
    KTH Royal Institute of Technology, Sweden.
    Löbmann, Korbinian
    University of Copenhagen, Denmark.
    Solid cellulose nanofiber based foams – Towards facile design of sustained drug delivery systems2016In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 244, p. 74-82Article in journal (Refereed)
    Abstract [en]

    Control of drug action through formulation is a vital and very challenging topic within pharmaceutical sciences. Cellulose nanofibers (CNF) are an excipient candidate in pharmaceutical formulations that could be used to easily optimize drug delivery rates. CNF has interesting physico-chemical properties that, when combined with surfactants, can be used to create very stable air bubbles and dry foams. Utilizing this inherent property, it is possible to modify the release kinetics of the model drug riboflavin in a facile way. Wet foams were prepared using cationic CNF and a pharmaceutically acceptable surfactant (lauric acid sodium salt). The drug was suspended in the wet-stable foams followed by a drying step to obtain dry foams. Flexible cellular solid materials of different thicknesses, shapes and drug loadings (up to 50 wt%) could successfully be prepared. The drug was released from the solid foams in a diffusion-controlled, sustained manner due to the presence of intact air bubbles which imparted a tortuous diffusion path. The diffusion coefficient was assessed using Franz cells and shown to be more than one order of magnitude smaller for the cellular solids compared to the bubble-free films in the wet state. By changing the dimensions of dry foams while keeping drug load and total weight constant, the drug release kinetics could be modified, e.g. a rectangular box-shaped foam of 8 mm thickness released only 59% of the drug after 24 h whereas a thinner foam sample (0.6 mm) released 78% of its drug content within 8 h. In comparison, the drug release from films (0.009 mm, with the same total mass and an outer surface area comparable to the thinner foam) was much faster, amounting to 72% of the drug within 1 h. The entrapped air bubbles in the foam also induced positive buoyancy, which is interesting from the perspective of gastroretentive drug-delivery.

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