Cholesteryl-cyclodextrins: synthesis and insertion into phospholipid membranes

Auzély‐Velty, Rachel; Perly, Bruno; Taché, Olivier; Zemb, Thomas; Jéhan, Philippe; Guénot, Pierre; Dalbiez, Jean‐Pierre; Djedaïni‐Pilard, Florence

doi:10.1016/s0008-6215(99)00086-5

Cited by 58 publications

(32 citation statements)

References 23 publications

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“…The peptide was cleaved from the resin and deprotected by treatment with trifluoroacetic acid (TFA)-ethanedithiol (EDT) (95 : 5), and purified by a reverse phase high-performance liquid chromatography (RP-HPLC). Introduction of β-CyD to the N-terminus of GABA-R8-amide was conducted using 6-deoxy-6-(N-hydroxysuccinimide)-β-CyD (NHS-CyD) 21) (5 equiv.) and N-methylmorpholine (2 equiv.)…”

Section: Methodsmentioning

confidence: 99%

Cholesterol-Lowering Effect of Octaarginine-Appended β-Cyclodextrin in <i>Npc1</i>-Trap-CHO Cells

Motoyama

Nishiyama

Maeda

et al. 2016

Biological & Pharmaceutical Bulletin

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Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disorder, which is an inherited disease characterized by the accumulation of unesterified cholesterol in endolysosomes. Recently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) has been used for the treatment of NPC, and ameliorated a hepatosplenomegaly in the patients. However, to obtain the treatment efficacy, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by using active intracellular delivery system of β-CyD to NPC cells is expected. In this study, to efficiently deliver β-CyD to NPC-like cells, we newly synthesized octaarginine (R8)-appended β-CyD with a spacer of γ-aminobutyric acid (R8-β-CyD) and evaluated its cytotoxicity, intracellular distribution, endocytosis pathway and cholesterol-lowering effect in Npc1-trap-Chinese hamster ovary (CHO) cells, cholesterol-accumulated cells through the impairment of NPC1 function. R8-β-CyD did not show cytotoxicity in the cells. In addition, Alexa568-labeled R8-β-CyD was actively internalized into Npc1-trap-CHO cells, possibly through micropinocytosis. Notably, R8-β-CyD significantly decreased intracellular cholesterol content compared with HP-β-CyD. These results suggest that R8-β-CyD may be a promising therapeutic agent for ameliorating cholesterol accumulation in NPC.

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Section: Methodsmentioning

confidence: 99%

Cholesterol-Lowering Effect of Octaarginine-Appended β-Cyclodextrin in <i>Npc1</i>-Trap-CHO Cells

Motoyama

Nishiyama

Maeda

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Grafting of hydrophobic moieties by reaction with the primary or secondary hydroxyl groups confers them an amphiphilic character. [171][172][173][174][175] Such amphiphilic compounds may self-organize in aqueous phase to form supramolecular assemblies. One such example is Chol-DIMEB (cholesterol -heptakis(2,6-di-O-methyl)-bCD): this molecule consists of a parent methylated bCD in which one of the anhydroglucose units is linked with cholesterol via its primary hydroxyl group through a succinic acid spacer.…”

Section: Self-assemble Of CD Complexesmentioning

confidence: 99%

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions

Ryzhakov

Thi

Stappaerts

et al. 2016

Journal of Pharmaceutical Sciences

114

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Cyclodextrins (CDs) are enabling pharmaceutical excipients that can be found in numerous pharmaceutical products worldwide. Because of their favorable toxicologic profiles, CDs are often used in toxicologic and phase I assessments of new drug candidates. However, at relatively high concentrations, CDs can spontaneously self-assemble to form visible microparticles in aqueous mediums and formation of such visible particles may cause product rejections. Formation of subvisible CD aggregates are also known to affect analytical results during product development. How and why these CD aggregates form is largely unknown, and factors contributing to their formation are still not elucidated. The physiochemical properties of CDs are very different from simple amphiphiles and lipophilic molecules that are known to self-assemble and form aggregates in aqueous solutions but very similar to those of linear oligosaccharides. In general, negligible amounts of aggregates are formed in pure CD solutions, but the aggregate formation is greatly enhanced on inclusion complex formation, and the extent of aggregation increases with increasing CD concentration. The diameter of the aggregates formed is frequently less than about 300 nm, but visible aggregates can also be formed under certain conditions.

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“…Grafting of hydrophobic moieties on the primary or the secondary faces of natural cyclodextrins (cyclic oligosaccharides forming nanocavity structures) confers them an amphiphilic character [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Synthesis of various modified cyclodextrins has been undertaken because such amphiphilic compounds may self-organize in aqueous phase to form supramolecular assemblies as drug carriers of high stability upon dilution [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Nano-Assemblies of Modified Cyclodextrins and Their Complexes with Guest Molecules: Incorporation in Nanostructured Membranes and Amphiphile Nanoarchitectonics Design

2014

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A variety of cyclodextrin-based molecular structures, with substitutions of either primary or secondary faces of the natural oligosaccharide macrocycles of α-, β-, or γ-cyclodextrins, have been designed towards innovative applications of self-assembled cyclodextrin nanomaterials. Amphiphilic cyclodextrins have been obtained by chemical or enzymatic modifications of their macrocycles using phospholipidyl, peptidolipidyl, cholesteryl, and oligo(ethylene oxide) anchors as well as variable numbers of grafted hydrophobic hydrocarbon or fluorinated chains. These novel compounds may self-assemble in an aqueous medium into different types of supramolecular nanoassemblies (vesicles, micelles, nanorods, nanospheres, and other kinds of nanoparticles and liquid crystalline structures). This review discusses the supramolecular nanoarchitectures, which can be formed by amphiphilic cyclodextrin derivatives in mixtures with other molecules (phospholipids, surfactants, and olygonucleotides). Biomedical applications are foreseen for nanoencapsulation of drug molecules in the hydrophobic interchain volumes and nanocavities of the amphiphilic cyclodextrins (serving as drug carriers or pharmaceutical excipients), anticancer phototherapy, gene delivery, as well as for protection of instable active ingredients through inclusion complexation in nanostructured media.

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Cholesteryl-cyclodextrins: synthesis and insertion into phospholipid membranes

Cited by 58 publications

References 23 publications

Cholesterol-Lowering Effect of Octaarginine-Appended β-Cyclodextrin in <i>Npc1</i>-Trap-CHO Cells

Cholesterol-Lowering Effect of Octaarginine-Appended β-Cyclodextrin in <i>Npc1</i>-Trap-CHO Cells

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions

Nano-Assemblies of Modified Cyclodextrins and Their Complexes with Guest Molecules: Incorporation in Nanostructured Membranes and Amphiphile Nanoarchitectonics Design

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