pH-Triggered nanostructural transformations in antimicrobial peptide/oleic acid self-assemblies

Abstract

The delivery of poorly water-soluble antimicrobial peptides (AMPs) that are sensitive to degradation is a major challenge in the pharmaceutical field. In this study, we design and characterize a pH-sensitive nanocarrier with the potential for delivery of AMPs and their protection from degradation. These nanobiointerfaces are prepared through the self-assembly of oleic acid (OA) with the human cathelicidin LL-37 in excess water. Advanced experimental methods including synchrotron small angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering were used to characterize the OA/LL-37 self-assemblies and their structural alterations in response to changes in pH and composition. Experimental findings reveal colloidal transformations from normal emulsions via micellar cubosomes and hexosomes to vesicles upon increasing the pH from 6.0 to 8.0 at a LL-37 content around 10 wt% relative to OA. Increasing the LL-37 content to 30 wt% in OA led to diminishing of micellar cubosomes and hexosomes in this narrow pH range, favoring the formation of micelles and vesicles of various shapes and sizes. Upon increasing the pH, with the strongest effect around pH 7.5, charge repulsions among the gradually deprotonating carboxylic groups of OA modified the geometric packing of the molecules, significantly affecting the nanostructure. These detailed insights into the formation of this unique family of nanobiointerfaces and their tunable structural features may contribute to the rational design of pH-responsive antimicrobial systems for the delivery of peptides, particularly poorly water-soluble AMPs.

Non-Lamellar Liquid Crystalline Nanocarriers for Thymoquinone Encapsulation

“…The identification of these phases presented in Figure 2A,B was based on the detection of the first three characteristic peaks for the former phase (reflections marked with blue solid arrows: (100), (110), and (200)) and at least nine characteristic Bragg peaks (reflections marked with black dash arrows: (111), (220), (311), (222), (400), (331), (422), (511), (333), (440)) for the latter phase. The inverse cubic Fd3m (Q 227 ) phase is a three-dimensional (3D) nanostructure enveloping quasi-spherical micelles with two different sizes and is the most identified micellar cubic phase in lipid systems [38,[42][43][44][45][46][47], and previously observed between the inverse hexagonal (H 2 ) and micellar (L 2 ) phases in both dispersed and non-dispersed systems based on binary mixtures of unsaturated monoglyceride (e.g., GMO, monolinolein, and monoelaidin) and solubilized oil (e.g., Vit E, oleic acid, tetradecane, and elaidic acid) [38,[44][45][46]. The lattice parameter of the coexisting second cubic Fd3m phase that was identified based on the detection of four weak reflections (marked with asterisk in Figure 2A).…”

Cubic Liquid Crystalline Nanostructures Involving Catalase and Curcumin: BioSAXS Study and Catalase Peroxidatic Function after Cubosomal Nanoparticle Treatment of Differentiated SH-SY5Y Cells

“…Regarding the lipid polymorphism, liquid crystalline phases have been formed by the self-assembly of hydrated mixtures of lyotropic lipids, co-lipids (oils or surfactants), and an aqueous phase, which may contain dissolved biomolecules (e.g., proteins, peptides or nucleic acids) [1,2,3,4,5,6,7,18,19,20,21,22,23,24,25,26,27,29,30,31,32,33,34,35,36]. Hydrated non-lamellar lipids (such as monoolein (MO)) can self-assemble into inverted bicontinuous cubic phases, bicontinuous sponge or inverted hexagonal phases depending on the experimental conditions and the applied stimuli [4,5,18,25,29,30,31,32].…”

“…Cubosome nanoparticles are fabricated upon dispersion of the bulk cubic liquid crystalline phases in excess aqueous medium [8,9,13,16,17,18,19,20,24]. The cubosome structure is sensitive to the incorporation of additives such as therapeutic molecules and diagnostic probes required for monitoring of the biomedical response to active targeting [9,16,18,21,35].…”

Supramolecular structures in lipid digestion and implications for functional food delivery

“…The encapsulation of degradation-sensitive molecules such as PUFAs, proteins, and peptides into these structures can protect them from degradation in the biological milieu, which may be crucial for facilitating their transport through the low-pH and protease-rich gastric fluid into the small intestine for absorption [55,59]. The solution conditions such as pH and ionic strength, that are significantly changing during digestion, are important to be taken into account as they affect the intermolecular forces and thereby modify the dynamic self-assembled structural features [47,53,60,61]. For instance, in pHtunable systems, the protonation and deprotonation of the fatty acids embedded in the waterelipid interface modify the geometric packing of the amphiphilic molecules, leading to significant alterations in the selfassembled structure.…”

“…For instance, switching from the protected mode to the active mode as the developed nanocarrier migrates from the stomach into the small intestine could be used to transport labile molecules through the harsh and degradative environment of the stomach to the small intestine for uptake into the circulatory system. Related to this, pH-responsive nanocarriers of antimicrobial peptides have been designed with the triolein digestion products glycerol monooleate and oleic acid as structure-forming molecules [53,55]. In this system, cubosomes did not interact with bacteria cells as the encapsulation of the antimicrobial peptides within the curved bilayers of the internal cubic phase in cubosomes was discussed to hinder their access to the bacterial membrane.…”