129850-62-0Relevant academic research and scientific papers
Syntheses of polycationic dendrimers on lipophilic peptide core for complexation and transport of oligonucleotides
Wimmer, Norbert,Marano, Robert J.,Kearns, Philip S.,Rakoczy, Elizabeth P.,Toth, Istvan
, p. 2635 - 2637 (2002)
Synthesis of novel polycationic lipophilic peptide core(s) was accomplished and these agents successfully transfected human retinal pigment epithelium cells with ODN1 upon complexation with the oligonucleotide. The level of transfection was indirectly measured by the decreased production of the protein hVEGF (human vascular endothelial growth factor) in comparison to the transfection agent cytofectin GSV.
Synthesis of a library of polycationic lipid core dendrimers and their evaluation in the delivery of an oligonucleotide with hVEGF inhibition
Parekh, Harendra S.,Marano, Robert J.,Rakoczy, Elizabeth P.,Blanchfield, Joanne,Toth, Istvan
, p. 4775 - 4780 (2007/10/03)
This article follows on from our previous work in the area of non-viral gene delivery using polycationic dendrimers (PCDs). Herein we report on the synthesis and efficacy of a new library of lipid core PCDs in the delivery of the anti-angiogenic oligonucleotide (ODN-1) to retinal pigment epithelial cells. ELISA was used to monitor hVEGF levels in cells transfected with dendriplexes, Cytofectin GSV and control (non-transfected). At 48 h, hVEGF titres had returned to that of the untransfected control for Cytofectin GSV however, a number of dendriplexes continued to exhibit a marked reduction in hVEGF titres.
Design, Synthesis, and Evaluation of a Liposaccharide Drug Delivery Agent: Application to the Gastrointestinal Absorption of Gentamicin
Ross, Benjamin P.,DeCruz, Shaun E.,Lynch, Thomas B.,Davis-Goff, Karen,Toth, Istvan
, p. 1251 - 1258 (2007/10/03)
The design, synthesis, and evaluation of a liposaccharide (11) for use as an agent to enhance the gastrointestinal absorption of charged, hydrophilic drugs with poor membrane permeability is reported. 11 was designed to possess both surfactant and ion-pairing properties and was conveniently synthesized from D-glucuronic acid (2) and N-Boc-lipoamino acid (5) precursors in eight steps in good yield. Isothermal titration microcalorimetry was used to determine the critical micelle concentration of 11 (in PBS) to be 2.09 ± 0.01 mM with an enthalpy of demicellization of 4.91 ± 0.11 kJ/mol. The ability of 11 to enhance the gastrointestinal absorption of the aminoglycoside antibiotic gentamicin (1), a hydrophilic polycation with negligible oral bioavailability, was assessed in vivo using rats. Rats dosed orally with a mixture of 11 (100 mg/kg) and 1 (60 mg/kg) had a statistically significant (P ≤ 0.034) increase in Cmax, AUC120, and percent absolute bioavailability (F) compared to control 1 (60 mg/kg) alone. The highest bioavailability (F = 9.1 ± 2.0%) was achieved by dosing with the mixture 11 (100 mg/kg) and 1 (15 mg/kg). This represents a 6-fold increase in bioavailability compared to the control (F = 1.4 ± 0.3%). These results suggest that the molar ratio of 1:11 may be critical in optimizing the delivery system, a finding ascribed in part to the ion-pairing properties of 11. The effect of 11 on the gastrointestinal mucosa was assessed using light microscopy to examine tissue samples from rats used in the pharmacokinetic study. No morphological changes were found in either the esophagi or duodena of the rats examined. One rat dosed with 11 (100 mg/kg) and 1 (60 mg/kg) exhibited slight gastric erosion, which could be attributed to 11.
Lipidic Peptides, I Synthesis, Resolution and Structural Elucidation of Lipidic Amino Acids and Their Homo- and Hetero-Oligomers
Gibbons, William A.,Hughes, Richard A.,Charalambous, Mario,Christodoulou, Marika,Szeto, Alice,et al.
, p. 1175 - 1183 (2007/10/02)
The α-amino acids with long alkyl side chains, the so-called lipidic amino acids 1a-e, and their homo-oligomers, the lipidic peptides 1p-aj, represent a class of compounds which combine the structural properties of peptides and proteins with the characteristics of lipids and membranes.The amino acids were synthesised from the appropriate alkyl bromide and diethyl acetamidomalonate.Resolution was made chemically, by forming diastereomers of the amino acid esters with an optically pure α-pinene derivative.The protected homo-oligomers were synthesised in solution with the assistance of a water-soluble carbodiimide coupling agent.In order to modify the physical and chemical properties of the peptides, a series of protected hetero-oligomers were prepared, by similar methods, incorporating either other amino acids (3a-d, 7a-i) or side-chain-substituted lipidic amino acids (6a-d).
