- Preparation and characterization of a novel organic-inorganic nanohybrid "cerasome" formed with a liposomal membrane and silicate surface
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A novel class of organic-inorganic hybrids, the so-called cerasomes, which have a bilayer vesicular structure and a silicate surface, has been synthesized by combination of sol-gel reaction and self-assembly of organoalkoxysilanes with a molecular structure analogous to lipids. We have synthesized two cerasome-forming organoalkoxysilanes, N-[N-(3-triethoxysilyl)propylsuccinamoyl] dihexadecylamine (1) and N,N-dihexadecyl-;N"-[6-[(3-triethoxysilyl) propyldimethylammonio]hexanoyl]glycinamide bromide (2), and investigated the synthetic conditions of the cerasomes and their structural characteristics. For the proamphi philic 1, the cerasome was obtained under restricted pH conditions where acid-catalyzed hydrolysis of the triethoxysilyl moiety proceeded without disturbing the vesicle formation. In contrast, the amphiphilic 2, additionally having a hydrophilic quaternary ammonium group, formed stable dispersions of the cerasome in a wide pH range. The hydrolysis behavior of the triethoxysilyl groups was monitored by 1H NMR spectroscopy. Morphology of the cerasomes having the liposomal vesicular structure was confirmed by TEM observations. Extent of the development of siloxane networks through condensation among the silanol groups on the cerasome surface was evaluated by using MALDI-TOF-MS spectrometry. Formation of oligomers of the cerasome-forming lipids in the vesicle was clearly confirmed. Due to the siloxane network formation, the cerasome showed remarkably high morphological stability compared with a reference liposome, as evaluated by surfactant dissolution measurements.
- Katagiri, Kiyofumi,Hashizume, Mineo,Ariga, Katsuhiko,Terashima, Takashi,Kikuchi, Jun-Ichi
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- Design of Ionizable Lipids to Overcome the Limiting Step of Endosomal Escape: Application in the Intracellular Delivery of mRNA, DNA, and siRNA
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The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from naturally occurring aminoglycoside tobramycin, was prepared using improved synthetic procedures that allow structural variations on the linker and hydrophobic domain levels. Complexes formed between the new ionizable lipids and mRNA, DNA, or siRNA were characterized by cryo-TEM experiments and their transfection potency was evaluated using different cell types. We demonstrated that lead molecule 30, bearing a biodegradable diester linker, formed small complexes with nucleic acids and provided very high transfection efficiency with all nucleic acids and cell types tested. The obtained results suggested that the improved and "universal" delivery properties of 30 resulted from an optimized endosomal escape, through the lipid-mixing mechanism.
- Habrant, Damien,Peuziat, Pauline,Colombani, Thibault,Dallet, Laurence,Gehin, Johan,Goudeau, Emilie,Evrard, Bérangère,Lambert, Olivier,Haudebourg, Thomas,Pitard, Bruno
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- Gadolinium DO3A derivatives mimicking phospholipids; preparation and in vitro evaluation as pH responsive MRI contrast agents
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A series of Gd-DO3A derivatives (8a-d) mimicking phospholipids have been prepared. Two of the complexes, Gd-HADB-DO3A (8a) and Gd-HADO-DO3A (8b), have been evaluated as pH responsive MRI contrast agents in vitro. The T1-relaxivity (r1/sub
- Hovland,Gl?ga?rd,Aasen,Klaveness
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- Liposomal nanohybrid cerasomes for mitochondria-targeted drug delivery
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Mitochondrial dysfunctions cause numerous human disorders and the development of mitochondria-targeted nanocarriers for drug delivery has aroused great attention. Herein, we report the synthesis of a liposomal nanohybrid cerasome modified with triphosphonium (TPP) for drug delivery to the mitochondrial matrix. The cerasomes were observed to possess an average size of about 38 nm in diameter, and the theoretical simulation of GBEMP mapping demonstrated that the amphiphilic organotrialkoxysilanes were stable as a bilayer equilibrium conformation after self-assembly. The cerasomes showed good stability, excellent biocompatibility and sustainable drug release behavior. Moreover, the TPP-targeted cerasomes resulted in greater drug accumulation in mitochondria, thus leading to a greater antitumor effect as compared to non-targeted cerasomes by using doxorubicin as a modal drug. The specific accumulation of TPP-targeted cerasomes within mitochondria was also confirmed by using JC-1 as the fluorescent probe to analyze the mitochondrial transmembrane potential change.
- Wang, Yanfang,Wang, Beibei,Liao, Han,Song, Xiaojie,Wu, Hao,Wang, Huihui,Shen, Hujun,Ma, Xiaojun,Tan, Mingqian
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- Selective Transformations of Triglycerides into Fatty Amines, Amides, and Nitriles by using Heterogeneous Catalysis
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The use of triglycerides as an important class of biomass is an effective strategy to realize a more sustainable society. Herein, three heterogeneous catalytic methods are reported for the selective one-pot transformation of triglycerides into value-added chemicals: i) the reductive amination of triglycerides into fatty amines with aqueous NH3 under H2 promoted by ZrO2-supported Pt clusters; ii) the amidation of triglycerides under gaseous NH3 catalyzed by high-silica H-beta (Hβ) zeolite at 180 °C; iii) the Hβ-promoted synthesis of nitriles from triglycerides and gaseous NH3 at 220 °C. These methods are widely applicable to the transformation of various triglycerides (C4–C18 skeletons) into the corresponding amines, amides, and nitriles.
- Jamil, Md. A. R.,Siddiki, S. M. A. Hakim,Touchy, Abeda Sultana,Rashed, Md. Nurnobi,Poly, Sharmin Sultana,Jing, Yuan,Ting, Kah Wei,Toyao, Takashi,Maeno, Zen,Shimizu, Ken-ichi
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p. 3115 - 3125
(2019/04/26)
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- Conversion of Primary Amines to Symmetrical Secondary and Tertiary Amines using a Co-Rh Heterobimetallic Nanocatalyst
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Symmetrical tertiary amines have been efficiently realized from amine and secondary amines via deaminated homocoupling with heterogeneous bimetallic Co2Rh2/C as catalyst (molar ratio Co:Rh=2:2). Unsymmetric secondary anilines were produced from the reaction of anilines with symmetric tertiary amines. The Co2Rh2/C catalyst exhibited very high catalytic activity towards a wide range of amines and could be conveniently recycled ten times without considerable leaching. (Figure presented.).
- Chung, Hyunho,Han, Seulgi,Chung, Young Keun,Park, Ji Hoon
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supporting information
p. 1267 - 1272
(2018/02/12)
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- A medicine silicon lipid ultrasound contrast agents in the preparation method and application of
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The invention provides a preparation method of a drug-loaded silicone grease ultrasonic contrast agent. The preparation method comprises fully dissolving silicone grease, polyethylene glycol phosphate derivatives and a fat-soluble anticancer drug in an organic solvent, adding water into the solution, carrying out whirling, removing the organic solvent, supplying water with a volume 3 times that of the solution into the solution, carrying out ultrasonic disintegration by an ultrasonic disintegrator, simultaneously and fast adding liquid fluorocarbon into the solution to obtain a pre-emulsion, and carrying out dialysis on the pre-emulsion in PBS for 1h to obtain a product. The preparation method has simple processes. The product has the average particle size of about 100nm and is conducive to aggregation at a tumor position by internal EPR effects. Siloxane silicone grease network distribution substantially improves structure stability and prolongs internal blood circulation time. Through HIFU, the drug-loaded silicone grease ultrasonic contrast agent release drugs at a local part of tumor tissue, drug treatment targeting is improved, HIFU treatment effects are substantially improved and HIFU-chemotherapy combined treatment is realized.
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Paragraph 0046; 0049
(2018/07/30)
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- Preparation method of silica body precursor-organosilane
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The invention discloses a preparation method of a silica body precursor-organosilane. The preparation method comprises the following steps that cetyl alcohol reacts with cetane amine to obtain biscetylamine; biscetylamine reacts with succinic anhydride and then reacts with aminopropyltriethoxysilane to obtain the silica body precursor-organosilane. The preparation method is simple in process, high in product yield and low in production cost and has an important application value.
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Paragraph 0030-0031
(2017/06/02)
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- NOVEL LIPIDS AND LIPID NANOPARTICLE FORMULATIONS FOR DELIVERY OF NUCLEIC ACIDS
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Compounds are provided having the following structure: (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8, R9, L1, L2, a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.
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- The C-and N-terminal residues of synthetic heptapeptide ion channels influence transport efficacy through phospholipid bilayers
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The synthetic peptide, R2N-COCH2OCH 2CO-Gly-Gly-Gly-PrO-Gly-Gly-Gly-OR′, was shown to be selective for Cl- over K+ when R is n-octadecyl and R′ is benzyl. Nineteen heptapeptides have now been prepared in which the N-terminal and C-terminal residues have been varied. All of the N-terminal residues are dialkyl but the C-terminal chains are esters, 2° amides, or 3° amides. The compounds having varied N-terminal anchors and C-terminal benzyl groups are as follows: 1, R = n-propyl; 2, R = n-hexyl; 3, R = n-octyl; 4, R = n-decyl; 5, R = n-dodecyl; 6, R = n-tetradecyl; 7, R = n-hexadecyl; 8, R = n-octadecyl. Compounds 9-19 have R = n-octadecyl and C-terminal residues as follows: 9, OR′ = OCH2CH3; 10, OR′ = OCH(CH 3)2; 11, OR′ = O(CH2)6CH 3; 12, OR′ = OCH2-c-C6H11; 13, OR′ = O(CH2)9CH3; 14, OR′ = O(CH2)17CH3; 15, NR′2 = N[(CH2)6CH3]2; 16, NHR′ = NH(CH2)9CH3; 17, NR′2 = N[(CH2)9CH3]2; 18, NHR′ = NH(CH2)17CH3; 19, NR′2 = N[(CH2)17CH3]2. The highest anion transport activities were observed as follows. For the benzyl esters whose N-terminal residues were varied, i.e. 1-8, compound 3 was most active. For the C18 anchored esters 10-14, n-heptyl ester 11 was most active. For the C18 anchored, C-terminal amides 15-19, di-n-decylamide 17 was most active. It was concluded that both the C-and N-terminal anchors were important for channel function in the bilayer but that activity was lost unless only one of the two anchoring groups was dominant. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.
- Djedovic, Natasha,Ferdani, Riccardo,Harder, Egan,Pajewska, Jolanta,Pajewski, Robert,Weber, Michelle E.,Schlesinger, Paul H.,Gokel, George W.
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p. 291 - 305
(2007/10/03)
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- Anchor dependency for non-glycerol based cationic lipofectins: Mixed bag of regular and anomalous transfection profiles
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Although detailed structure-activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure-activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1-15) of recently reported non-glycerol based monocationic transfection lipids. The C14 analogues in both series 1 (lipids 1-6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C10 and C14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure-activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane re-organizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1-15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37°C).
- Singh, Rajkumar Sunil,Mukherjee, Koushik,Banerjee, Rajkumar,Chaudhuri, Arabinda,Hait, Samik Kumar,Moulik, Satya Priya,Ramadas, Yerramsetti,Vijayalakshmi, Amash,Rao, Nalam Madhusudhana
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p. 900 - 909
(2007/10/03)
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- Polyamide oligomers
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The present invention relates to new polyamide oligomers. These oligomers can be conjugated to lipids, nucleic acids, peptides, proteins, etc. The oligomer-lipid conjugates can be used to form liposomes, virusomes, micelles, etc., optionally containing drugs or biological agents. The polyamide oligomers are heterobifunctional allowing the attachment of other suitable ligand compounds (e.g., a targeting moiety). In addition, methods of use for the liposomes, virusomes, micelles, etc., are provided.
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- Design, synthesis, and transfection biology of novel cationic glycolipids for use in liposomal gene delivery
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The molecular structure of the cationic lipids used in gene transfection strongly influences their transfection efficiency. High transfection efficiencies of non-glycerol-based simple monocationic transfection lipids with hydroxyethyl headgroups recently reported by us (Banerjee et al. J. Med. Chem. 1999, 42, 4292-4299) are consistent with the earlier observations that the presence of hydroxyl functionalities in the headgroup region of a cationic lipid contributes favorably in liposomal gene delivery. Using simple sugar molecules as the source of multiple hydroxyl functionalities in the headgroup region of the transfection lipids, we have synthesized four novel simple monocationic transfection lipids, namely, 1-deoxy-1-[dihexadecyl(methyl)-ammonio]-D-xylitol (1), 1-deoxy-1-[methyl(ditetradecyl)ammonio]-D-arabinitol (2), 1-deoxy-1-[dihexadecyl(methyl)ammonio]-D-arabinitol (3) and 1-deoxy-1-[methyl(dioctadecyl)ammonio]-D-arabinitol (4), containing hydrophobic aliphatic tails and the hydrophilic arabinosyl or xylose sugar groups linked directly to the positively charged nitrogen atom. Syntheses, chemical characterizations, and the transfection biology of these novel transfection lipids 1-4 are described in this paper. Lipid 1, the xylosyl derivative, showed maximum transfection on COS-1 cells. All the lipids showed transfection with cholesterol as colipid and not with dioleoylphosphatidylethanolamine (DOPE). Radioactive quantitation of free and complexed DNA combined with ethidium bromide exclusion measurements suggest that though nearly 70% of the DNA exists as complexed DNA, the DNA may not have condensed as was observed with other cationic lipids. Presence of additional (more than two) hydroxyl functionalities in the headgroup of the cationic lipids appears to have improved the transfection efficiency and made these lipids less cytotoxic compared to two-hydroxyl derivatives.
- Banerjee,Mahidhar,Chaudhuri,Gopal,Rao
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p. 4176 - 4185
(2007/10/03)
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- A new strategy for the preparation of secondary amines via o- (tetrahydropyranyloxymethyl)-benzamides
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The new synthesis strategy for the preparation of secondary amines starts from N-alkyl-phthalimides which are reduced to the corresponding o- hydroxymethyl-N-alkyl-benzamides. After protection of the hydroxy group as tetrahydropyranyl ether the N-alkyl-benzamides are alkylated to o- (tetrahydropyranyloxymethyl)-N,N-dialkyl-benzamides. The deprotection of the hydroxy group and the release of the secondary amines can be achieved in execellent yields in one reaction step using aqueous acetic acid.
- Fichert, Thomas,Massing, Ulrich
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p. 5017 - 5018
(2007/10/03)
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- Molecular recognition of nucleotides by the guanidinium unit at the surface of aqueous micelles and bilayers. A comparison of microscopic and macroscopic interfaces
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Molecular recognition of the guanidinium/phosphate pair was investigated at microscopic interfaces of aqueous micelles and bilayers. Monoalkyl and dialkyl amphiphiles with guanidinium head groups were synthesized and dispersed in water to form micelles and bilayers having guanidinium groups at the aggregate surface. Binding of nucleotides such as AMP to these functionalized aggregates was evaluated by using an equilibrium dialysis (ultrafiltration) method. The observed binding constants of 102-104 M-1 are much larger than the corresponding binding constant reported for a monomerically dispersed pair in the aqueous phase (1.4 M-1) but are smaller than those found at the macroscopic air-water interface (106-107 M-1). Therefore, the macroscopic interface promotes guanidinium-phosphate interaction more effectively than the microscopic interface. The present finding indicates that the microscopic interface can strengthen hydrogen bonding and/or electrostatic interaction even in the presence of water. Saturation binding phenomena were different between micelles and bilayers. All of the guanidinium groups in fluid micelles are effective for phosphate binding, but part of the guanidinium group in bilayers are not effective probably because of steric restriction.
- Onda,Yoshihara,Koyano,Ariga,Kunitake
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p. 8524 - 8530
(2007/10/03)
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- Xylene-diamines as antiviral agents
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Compounds of the formula STR1 or a non-toxic acid addition salt thereof wherein R1 is alkyl of from 1 to 20 carbon atoms; R2 is alkyl of from 12 to 20 carbon atoms; R3 is selected from the group consisting of hydrogen and hydroxyalkyl of from 2 to 8 carbon atoms; and R4 is selected from the group consisting of hydrogen, alkyl of from 1 to 8 carbon atoms and hydroxyalkyl of from 2 to 8 carbon atoms, said compounds are useful for combating viral infections in vertebrate animals.
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