Multifunctional Nano‐Biointerfaces: Cytocompatible Antimicrobial Nanocarriers from Stabilizer‐Free Cubosomes

Abstract

The rational design of alternative antimicrobial materials with reduced toxicity toward mammalian cells is highly desired due to the growing occurrence of bacteria resistant to conventional antibiotics. A promising approach is the design of lipid-based antimicrobial nanocarriers. However, most of the commonly used polymer-stabilized nanocarriers are cytotoxic. Herein, the design of a novel, stabilizer-free nanocarrier for the human cathelicidin derived antimicrobial peptide LL-37 that is cytocompatible and promotes cell proliferation for improved wound healing is reported. The nanocarrier is formed through the spontaneous integration of LL-37 into novel, stabilizer-free glycerol monooleate (GMO)-based cubosomes. Transformations in the internal structure of the cubosomes from Pn3m to Im3m-type and eventually their transition into small vesicles and spherical micelles are demonstrated upon the encapsulation of LL-37 into their internal bicontinuous cubic structure using small angle X-ray scattering, cryogenic transmission electron microscopy, and light scattering techniques. Additional in vitro biological assays show the antimicrobial activity of the stabilizer-free nano-objects on a variety of bacteria strains, their cytocompatibility, and cell-proliferation enhancing effect. The results outline a promising strategy for the comprehensive design of antimicrobial, cytocompatible lipid nanocarriers for the protection and delivery of bioactive molecules with potential for application as advanced wound healing materials.

Non-Lamellar Liquid Crystalline Nanocarriers for Thymoquinone Encapsulation

“…Taking into account the current interest in the development of nanocarriers for delivering TQ and other phytochemicals [8][9][10][11][15][16][17][18][19][20][21], here we focus on non-lamellar liquid crystalline nanoparticles enveloping a biphasic feature of inverse discontinuous cubic (I 2 ) phase of the symmetry Fd3m phase coexisting with an inverse hexagonal (H 2 ) phase for TQ encapsulation. The unique structural properties of these nano-self-assemblies and their analogues [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] render them particularly attractive for enhancing the solubilization capacity of poorly water-soluble drugs and improving their delivery through different routes of administration [23,26,27,29,36]. However, the structural features of this family of liquid crystalline nanoparticles is highly sensitive to drug loading, and subsequently could affect its stability as well as biological performance.…”

Self-assembly of glycerol monooleate with the antimicrobial peptide LL-37: a molecular dynamics study

“…The latter corresponds to a GMO/LL-37 weight ratio of 1 : 1 that was also used in previous experimental studies. 45 Aer a simulation time of 24 ns, the GMO molecules separated from the solvent and formed small aggregates that were used as a reference for the following simulations with GMO and LL-37. The GMO aggregates displayed a surface with hydrophilic (hydroxyl groups from the glycerol head) and hydrophobic (aliphatic chains) domains, see Fig.…”

“…The number of LL-37 to GMO was chosen to have a 1 : 1 wt ratio as the corresponding experiments. 45 Initially, the two simulations were started from a random conguration of the molecules in a cubic box generated using Packmol. 67 To insert the molecules in the system, the minimum distance (tolerance) between the atoms in the different molecules was set to 2.3Å.…”

“…6a, display signicant differences. 45 Below q of 0.1Å À1 the simulated I(q) does not display any correlation with the experimental data because the size of the simulated systems is smaller than 50Å, as shown in Fig. 6b and c. Instead, in this region, the constant overall scattering from the micelles was observed in the simulated I(q) curve, while the experimental curve has a hump around q $ 0.04 A À1 , a minimum at q $ 0.02Å À1 and then increases again at lower q.…”

“…Together with the shuttle mechanism in the GMO/LL-37 nanostructures, this change in entropy may also contribute to the previously reported increase in the antimicrobial activity of the LL-37 in this complex in experimental studies. 26,45…”