Detailed Structure of Diamond-Type Lipid Cubic Nanoparticles

Abstract

Supramolecular three-dimensional self-assembly of nonlamellar lipids with fragments of the protein immunoglobulin results in a bicontinuous cubic phase fragmented into nanoparticles with open water channels (cubosomes). The structure of the diamond-type cubic nanoparticles is characterized experimentally by freeze-fracture electron microscopy, and it is mathematically modeled with nodal surfaces emphasizing the fluid-like undulations of the cubosomic interfaces. Based on scaling-up and scaling-down approaches, we present stable and intermediate-kind nanoparticles resulting from the cubosomic growth. Our results reveal the smallest stable diamond-type cubosomic entity that can serve as a building block of more complex nanostructured fluid drug delivery vehicles of therapeutic proteins. The evidence presented for lipid-bilayer undulations in the surface region of the protein/lipid cubosomes could have important consequences for possible applications of these hierarchically organized porous nanoparticles.

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

“…59,60 Toward mimicking the physiological conditions for protein drug delivery, the research is being extended to fully hydrated cubic lipid systems for protein nanoconfinement. 11,14,50,56,[64][65][66][67][68][69][70] …”

“…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.…”

“…Indeed, the diamond-type cubic particle involves two networks of aqueous channels. 11 Upon contact with the medium containing dissolved biomolecules, one of the nanochannel networks is open, while the other is closed. Such an asymmetry may have a role in the protein entrapment through the pockets in the cubic structure.…”

“…[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.…”

Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies

“…Here, the secondary cubic nanoparticles or derivative vehicles like micelles may facilitate further contact with the cell membrane and increase absorption. [41][42][43][44][45] Piperine has the potential to interact with co-administered drugs (ie, drug-herb interaction) through inhibition of metabolism of the drug mediated by cytochrome P450 enzymes. 46 When the rats were treated with PPD-cubosome loaded with piperine, the cumulative absorption of PPD into the general circulation was adequately increased.…”