Membrane interactions of microgels as carriers of antimicrobial peptides

• Microgels are interesting as potential delivery systems for antimicrobial peptides. In order to elucidate membrane interactions of such systems, we here investigate effects of microgel charge density on antimicrobial peptide loading and release, as well as consequences of this for membrane interactions and antimicrobial effects, using ellipsometry, circular dichroism spectroscopy, nanoparticle tracking analysis, dynamic light scattering and z-potential measurements. Anionic poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate considerable amounts of the cationic antimicrobial peptides LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW) and to protect incorporated peptides from degradation by infection-related proteases at high microgel charge density. As a result of their net negative z-potential also at high peptide loading, neither empty nor peptide-loaded microgels adsorb at supported bacteria-mimicking membranes. Instead, membrane disruption is mediated almost exclusively by peptide release. Mirroring this, antimicrobial effects against several clinically relevant bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa) were found to be promoted by factors facilitating peptide release, such as decreasing peptide length and decreasing microgel charge density. Microgels were further demonstrated to display low toxicity towards erythrocytes. Taken together, the results demonstrate some interesting opportunities for the use of microgels as delivery systems for antimicrobial peptides, but also highlight several key factors which need to be controlled for their successful use. 

Subject headings

NATURVETENSKAP  -- Kemi (hsv//swe)

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

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

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

TEKNIK OCH TEKNOLOGIER  -- Medicinteknik -- Medicinsk material- och protesteknik (hsv//swe)

ENGINEERING AND TECHNOLOGY  -- Medical Engineering -- Medical Materials (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

Antimicrobial peptide

Drug delivery

Lipid membrane

Microgel

Bacteria

Charge density

Circular dichroism spectroscopy

Dichroism

Drug interactions

Escherichia coli

Gels

Light scattering

Membranes

Microorganisms

Polypeptides

Anti-microbial effects

Cationic antimicrobial peptides

Lipid membranes

Methicillin-resistant staphylococcus aureus

Nanoparticle tracking analysis

Pseudomonas aeruginosa

Peptides

anion

cathelicidin antimicrobial peptide LL 37

cation

dpk 060

drug carrier

poly(acrylate methacrylate)

poly(ethyl methacrylate)

polypeptide antibiotic agent

proteinase

triton x 100

unclassified drug

adsorption kinetics

analytic method

aqueous solution

Article

bacterial membrane

bactericidal activity

binding kinetics

cell interaction

circular dichroism

conformational transition

controlled study

cytotoxicity

drug delivery system

drug distribution

drug release

electrical parameters

ellipsometry

erythrocyte

gel

hemolysis assay

hydrophobicity

in vitro study

ionic strength

membrane damage

methicillin resistant Staphylococcus aureus

minimum inhibitory concentration

nanoencapsulation

nonhuman

particle size

photon correlation spectroscopy

priority journal

protein degradation

protein secretion

protein stability

static electricity

zeta potential

Antimicrobial peptide

Drug delivery

Lipid membrane

Microgel

Publication and Content Type

ref (subject category)

art (subject category)