Small-Angle Neutron and X-ray Scattering from Amphiphilic Stimuli-Responsive Diamond-Type Bicontinuous Cubic Phase

Abstract

The structural evolution of a diamond-type bicontinuous lipid cubic phase upon application of thermal and chemical (hydration agent) stimuli is investigated by means of small-angle neutron (SANS) and X-ray scattering (SAXS). The soft-matter cubic architecture responds by dramatic swelling (DLarge cubic structure) upon incorporation of a hydration-enhancing guest component (octyl glucoside) at low and ambient temperatures, the aqueous channel diameter increasing twice to approximately 7 nm. DLarge appears to be built up from an assembly of cubosomic domains, which may coexist with an amphiphilic lamellae domain at low temperatures. The chemical stimulus concentration can be selected as to tune the hydration of the nanochannels in the DLarge phase and its transformation into a DNormal phase at temperatures above the body temperature. Two-dimensional SANS images recorded upon heating scan reveal growth of spontaneously oriented domains of single-crystal cubic nature. Phase separation and squeezing out the guest-hydrating agent from the higher-curvature regions of the amphiphilic bilayer suggest a possible mechanism for the established transformations. The order-order structural transition, cubic DLarge-cubic DNormal, is found to be reversible upon cooling. The obtained results put forward a structure-based concept for release of encapsulated guest molecules from stimuli-responsive and self-regulated cubosomic nanocarriers.

Self-Assembled Multicompartment Liquid Crystalline Lipid Carriers for Protein, Peptide, and Nucleic Acid Drug Delivery

“…Tuning of the aqueous nanochannel sizes ( Figure 4) constitutes a means for control of their encapsulation capacity for biomolecules. In order to get insight into the mechanism of nanoconfinement of protein, peptides, or DNA in labyrinthine cubic network structures, [10][11][12][13][14][15][45][46][47][48][49][50][57][58][59] we discuss the monoolein cubic phase swelling as related to the changes in the lipid membrane curvature. The spontaneous monolayer curvature of the monoglyceride lipid assemblies is negative.…”

“…12,46,47,66 The monolayer curvature is reduced upon accommodation of such surfactant molecules at the apolar/polar interface and the aqueous nanochannels are enlarged ( Figure 4B). This corresponds to a cubic phase swelling and a structural change to a less curved structure with larger water channels 46 (D w ≈ 7 nm).…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The investigations, by means of time-resolved SAXS, of the dynamic topological transitions of selfassembled amphiphilic mixtures have allowed the discovery of lipid-based nanocarriers with tunable internal organizations and nanochannel sizes. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The phase states of nonlamellar lipids, amphiphilic mixtures with lipopolymers or lipophilic conjugates, such as peptide surfactants, squalenoyl (SQ) derivatives, and acylated and peptidolipidyl-modified cyclodextrins, have been studied toward the design of novel controlled drug delivery nanocarriers with enhanced performance.…”

“…These energies are functions of the curvature, thickness, and rigidity of the lipid membrane. In general, multicompartment amphiphilic structures can be produced by self-assembly of (i) mixtures involving lipids with nonlamellar propensity, 5,6,9,[11][12][13][14][15]17,18,33,[35][36][37][38][39][40][41][46][47][48][49][50] (ii) mixtures of amphiphiles and hybrid lipid derivatives with nonlamellar properties, for instance, squalenoyl compounds, 4,20 or (iii) lipid/peptide self-assemblies forming inverted-phase LC nanostructures. 51,52 Nonionic lipids, such as glycerol monooleate (MO) (Figure 2), are suitable for protein stabilization.…”

“…51,52 Nonionic lipids, such as glycerol monooleate (MO) (Figure 2), are suitable for protein stabilization. [10][11][12][13][14][35][36][37][48][49][50]54,55 The self-assembled MO/water LC phases 9,11,38,54,[57][58][59][60][61] represent a biocompatible, nanostructured lipid membrane medium with tunable hydration, which offers new opportunities for design of protein and peptide carriers with multicompartment architecture and controlled release properties. 10,16,19,26,55,57 The thermoreversible lamellarto-cubic phase transitions of polar monoglyceride lipids have attracted huge research interest 5,6,9,12,13,15,17,18,[38][39][40] in view of various applications including peptide and protein drug delivery.…”