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Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices.

Allain V, Bourgaux C, Couvreur P - Nucleic Acids Res. (2011)

Bottom Line: This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly.Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids.Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris-Sud 11, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.

ABSTRACT
This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base-base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

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Schematic representation of the structure of lamellar and hexagonal lipid–DNA complexes. The lamellar phase Lαc exhibits DNA rods intercalated between lipid bilayers. The hexagonal phase HIc consists of DNA rods between rodlike lipid micelles arranged on a hexagonal lattice. The inverse hexagonal HIIc phase consists of DNA rods coated with a lipid monolayer arranged on a hexagonal lattice. The lipids are in red (headgroup) and grey (chain) and the DNA rods are in blue [redrawn from Ref. (61)].
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gkr681-F4: Schematic representation of the structure of lamellar and hexagonal lipid–DNA complexes. The lamellar phase Lαc exhibits DNA rods intercalated between lipid bilayers. The hexagonal phase HIc consists of DNA rods between rodlike lipid micelles arranged on a hexagonal lattice. The inverse hexagonal HIIc phase consists of DNA rods coated with a lipid monolayer arranged on a hexagonal lattice. The lipids are in red (headgroup) and grey (chain) and the DNA rods are in blue [redrawn from Ref. (61)].

Mentions: The aim of gene therapy is to cure inherited or acquired genetic disorder or diseases, including cancer, by replacing or inhibiting the faulting gene in cells, using natural or synthetic nucleic acids. The delivery to cells of DNA, antisense oligonucleotides or si-RNA, requires a vector such as lipoplexes. The majority of lipoplexes consists of nucleic acids mixed with cationic lipids in the presence of a ‘helper’ lipid, usually dioleoylphosphatidylethanolamine (DOPE) or dioleoylphosphatidylcholine (DOPC). In this approach, the negatively charged DNA interacts through electrostatic forces with the positively charged lipid. Structural studies have shown that DNA can be complexed into lamellar or hexagonal lipid phases (Figure 4). The addition of the ‘helper’ lipid favours the inverse hexagonal phase, which has been suggested to enhance transfection. The transfection efficiency of lamellar cationic lipoplexes depends on the charge density of lipid membranes, probably because of their electrostatic interactions with cells. In the regime of optimal membrane charge density, maximum in transfection efficiency was obtained when bilayers were made of a multicomponent lipid mixture, highlighting the importance of carrier lipidic composition (23). Unfortunately, after administration, the positive charges of the cationic lipids were demonstrated to dramatically interact with serum proteins, resulting in their fast elimination from the blood flow. Another drawback is the common cytotoxicity of cationic formulations due to cell membrane destabilization. Alternative delivery systems, bearing fewer charges, are thus considered in an attempt to overcome these problems. For instance, new lipids containing in their polar head thiourea functions, known as strong hydrogen bond donors, have been developed. Lipopolythioureas were capable of compacting DNA thanks to multiple hydrogen bonds involving the DNA phosphate groups. Moreover, the presence of the three forms of the thiourea function (i.e. thiourea, iminothiol and charged thiourea), afforded in vitro transfection of the lipids/ DNA complexes (24–26).Figure 4.


Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices.

Allain V, Bourgaux C, Couvreur P - Nucleic Acids Res. (2011)

Schematic representation of the structure of lamellar and hexagonal lipid–DNA complexes. The lamellar phase Lαc exhibits DNA rods intercalated between lipid bilayers. The hexagonal phase HIc consists of DNA rods between rodlike lipid micelles arranged on a hexagonal lattice. The inverse hexagonal HIIc phase consists of DNA rods coated with a lipid monolayer arranged on a hexagonal lattice. The lipids are in red (headgroup) and grey (chain) and the DNA rods are in blue [redrawn from Ref. (61)].
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3300006&req=5

gkr681-F4: Schematic representation of the structure of lamellar and hexagonal lipid–DNA complexes. The lamellar phase Lαc exhibits DNA rods intercalated between lipid bilayers. The hexagonal phase HIc consists of DNA rods between rodlike lipid micelles arranged on a hexagonal lattice. The inverse hexagonal HIIc phase consists of DNA rods coated with a lipid monolayer arranged on a hexagonal lattice. The lipids are in red (headgroup) and grey (chain) and the DNA rods are in blue [redrawn from Ref. (61)].
Mentions: The aim of gene therapy is to cure inherited or acquired genetic disorder or diseases, including cancer, by replacing or inhibiting the faulting gene in cells, using natural or synthetic nucleic acids. The delivery to cells of DNA, antisense oligonucleotides or si-RNA, requires a vector such as lipoplexes. The majority of lipoplexes consists of nucleic acids mixed with cationic lipids in the presence of a ‘helper’ lipid, usually dioleoylphosphatidylethanolamine (DOPE) or dioleoylphosphatidylcholine (DOPC). In this approach, the negatively charged DNA interacts through electrostatic forces with the positively charged lipid. Structural studies have shown that DNA can be complexed into lamellar or hexagonal lipid phases (Figure 4). The addition of the ‘helper’ lipid favours the inverse hexagonal phase, which has been suggested to enhance transfection. The transfection efficiency of lamellar cationic lipoplexes depends on the charge density of lipid membranes, probably because of their electrostatic interactions with cells. In the regime of optimal membrane charge density, maximum in transfection efficiency was obtained when bilayers were made of a multicomponent lipid mixture, highlighting the importance of carrier lipidic composition (23). Unfortunately, after administration, the positive charges of the cationic lipids were demonstrated to dramatically interact with serum proteins, resulting in their fast elimination from the blood flow. Another drawback is the common cytotoxicity of cationic formulations due to cell membrane destabilization. Alternative delivery systems, bearing fewer charges, are thus considered in an attempt to overcome these problems. For instance, new lipids containing in their polar head thiourea functions, known as strong hydrogen bond donors, have been developed. Lipopolythioureas were capable of compacting DNA thanks to multiple hydrogen bonds involving the DNA phosphate groups. Moreover, the presence of the three forms of the thiourea function (i.e. thiourea, iminothiol and charged thiourea), afforded in vitro transfection of the lipids/ DNA complexes (24–26).Figure 4.

Bottom Line: This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly.Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids.Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris-Sud 11, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.

ABSTRACT
This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base-base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

Show MeSH