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Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide
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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.

Place, publisher, year, edition, pages
2018. Vol. 522, p. 126-135
Keywords [en]
AP114, Antimicrobial peptide, Cubosome, Freeze-drying, Glycerol monooleate, Hexosome, Liquid crystal, Plectasin
National Category
Physical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-353471DOI: 10.1016/j.jcis.2018.03.062ISI: 000431100000015PubMedID: 29587194OAI: oai:DiVA.org:uu-353471DiVA, id: diva2:1217734
Funder
EU, FP7, Seventh Framework Programme, 604182Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-07-25Bibliographically approved

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Edwards, Katarina

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