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

• 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.

Ämnesord

NATURVETENSKAP  -- Kemi -- Oorganisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Inorganic Chemistry (hsv//eng)

NATURVETENSKAP  -- Kemi -- Fysikalisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Physical Chemistry (hsv//eng)

NATURVETENSKAP  -- Kemi -- Annan kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Other Chemistry Topics (hsv//eng)

Nyckelord

Antimicrobial peptide

AP114

Cubosome

Freeze-drying

Glycerol monooleate

Hexosome

Liquid crystal

Plectasin

Drying

Dynamic light scattering

Glycerol

High resolution transmission electron microscopy

Hydration

Liquid crystals

Low temperature drying

Microorganisms

Nanoparticles

Particle size

Particle size analysis

Peptides

Powders

Size distribution

Targeted drug delivery

Transmission electron microscopy

X ray scattering

Cubosomes

Freeze drying

Controlled drug delivery

ap 114

disaccharide

lactose

nanoparticle

polypeptide antibiotic agent

sucrose

trehalose

unclassified drug

Article

bactericidal activity

drug delivery system

drug formulation

drug release

in vitro study

kinetics

molecular stability

nonhuman

phase transition

photon correlation spectroscopy

powder

priority journal

X ray crystallography

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