Self-Assembled Multicompartment Liquid Crystalline Lipid Carriers for Protein, Peptide, and Nucleic Acid Drug Delivery.
Summary of "Self-Assembled Multicompartment Liquid Crystalline Lipid Carriers for Protein, Peptide, and Nucleic Acid Drug Delivery."
Lipids and lipopolymers self-assembled into biocompatible nano- and mesostructured functional materials offer many potential applications in medicine and diagnostics. In this Account, we demonstrate how high-resolution structural investigations of bicontinuous cubic templates made from lyotropic thermosensitive liquid-crystalline (LC) materials have initiated the development of innovative lipidopolymeric self-assembled nanocarriers. Such structures have tunable nanochannel sizes, morphologies, and hierarchical inner organizations and provide potential vehicles for the predictable loading and release of therapeutic proteins, peptides, or nucleic acids. This Account shows that structural studies of swelling of bicontinuous cubic lipid/water phases are essential for overcoming the nanoscale constraints for encapsulation of large therapeutic molecules in multicompartment lipid carriers. For the systems described here, we have employed time-resolved small-angle X-ray scattering (SAXS) and high-resolution freeze-fracture electronic microscopy (FF-EM) to study the morphology and the dynamic topological transitions of these nanostructured multicomponent amphiphilic assemblies. Quasi-elastic light scattering and circular dichroism spectroscopy can provide additional information at the nanoscale about the behavior of lipid/protein self-assemblies under conditions that approximate physiological hydration. We wanted to generalize these findings to control the stability and the hydration of the water nanochannels in liquid-crystalline lipid nanovehicles and confine therapeutic biomolecules within these structures. Therefore we analyzed the influence of amphiphilic and soluble additives (e.g. poly(ethylene glycol)monooleate (MO-PEG), octyl glucoside (OG), proteins) on the nanochannels' size in a diamond (D)-type bicontinuous cubic phase of the lipid glycerol monooleate (MO). At body temperature, we can stabilize long-living swollen states, corresponding to a diamond cubic phase with large water channels. Time-resolved X-ray diffraction (XRD) scans allowed us to detect metastable intermediate and coexisting structures and monitor the temperature-induced phase sequences of mixed systems containing glycerol monooleate, a soluble protein macromolecule, and an interfacial curvature modulating agent. These observed states correspond to the stages of the growth of the nanofluidic channel network. With the application of a thermal stimulus, the system becomes progressively more ordered into a double-diamond cubic lattice formed by a bicontinuous lipid membrane. High-resolution freeze-fracture electronic microscopy indicates that nanodomains are induced by the inclusion of proteins into nanopockets of the supramolecular cubosomic assemblies. These results contribute to the understanding of the structure and dynamics of functionalized self-assembled lipid nanosystems during stimuli-triggered LC phase transformations.
CNRS UMR8612 Physico-chimie-Pharmacotechnie-Biopharmacie, Univ Paris Sud , Châtenay-Malabry, F-92296 France.
This article was published in the following journal.
Name: Accounts of chemical research
Medical and Biotech [MESH] Definitions
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES.
Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES.
Conditions characterized by abnormal lipid deposition due to disturbance in lipid metabolism, such as hereditary diseases involving lysosomal enzymes required for lipid breakdown. They are classified either by the enzyme defect or by the type of lipid involved.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
The encapsulation and release of peptides, proteins, nucleic acids, and drugs in nanostructured lipid carriers depend on the type of the self-assembled liquid-crystalline organization and the structur...
Investigation of nonlamellar nanoparticles formed by dispersion of self-assembled lipid liquid crystalline phases is stimulated by their many potential applications in science and technology; resultin...
Lipid crystallization is ubiquitous in nature, observed in biological structures as well as in commercial products and applications. In a dehydrated state most of the lipids form well ordered crystals...
A metal (Ag, Au, Pd, Sn, Bi, In, Co, Al) layer directly deposited onto a liquid-crystalline lipid membrane resulted in different morphologies, ranging from a monolayer of discrete particles to a conti...
The role of the digestion of lipids in facilitating absorption of poorly water-soluble compounds, such as vitamins, is not only an important nutritional issue but is increasingly being recognized as a...
Women with a BRCA1 mutation face a lifetime risk of breast cancer of approximately 70% and a lifetime risk of ovarian cancer of approximately 40%. A number of potential anti-cancer nutrien...
Individuals submitted to a high-fat or a high-fructose/sucrose diet develop, over a 6 day-period, several features of the metabolic syndrome, including increased plasma triglycerides, incr...
To collect and analyze data on female carriers of severe and moderate hemophilia A and B.
RATIONALE: Collecting information about HTLV-1 carriers and HTLV-1 associated illnesses in blood donors in Jamaica may help doctors learn more about these diseases. PURPOSE: This clinical...
This was a prospective, randomised, open comparative monocentric phase IIIb study to evaluate the convenience, safety and efficacy of follitropin alfa (Gonal-f) liquid pen compared with fo...