Amphiphilic RGD and GHK peptides synergistically enhance liposomal delivery into cancer and endothelial cells

This study reveals enhanced cancer-targeting properties of a peptide composition consisting of RGD and GHK, recognized as an important cell adhesion factor and pleiotropic modulator of cellular functions, respectively. C12-GGRGD-NH2 and C12-GGGHK-NH2 amphiphilic peptides comprising a lauric acid moiety capable of insertion into the liposomal membrane were synthesized. Composite liposomes made of phosphatidylcholine, cationic DOTAP and the peptide(s) were used at a pre-optimized PC : DOTAP ratio of 35 : 1 and relative peptide content of 4 mol%. The RGD/GHK dual targeting system exhibited a profound synergistic effect on the cellular uptake of the liposomal formulation in integrin-overexpressing cancer and endothelial cells. Effective liposome activation via in situ association of the amphiphilc peptide(s) with the liposomal membrane was carried out. Dual peptide-modified liposomes loaded with doxorubicin or paclitaxel induced enhanced cytotoxicity accompanied by oxidative stress and mitochondria depolarization in the target cells. The study shows joint potential of RGD and GHK tripeptides as a targeting system in anticancer/antiangiogenic therapy and provides a methodology for screening of combinatorial effects of bioactive peptides displayed on the liposome surface. Peptide-modified liposomes were employed to reveal GHK-heparin binding, suggesting a potential complementary role of glycosaminoglycans in RGD/GHK-mediated liposomal delivery. This journal i

Cationic liposomes mediated transdermal delivery of meloxicam and ketoprofen: Optimization of the composition, in vitro and in vivo assessment of efficiency

New liposomes modified with pyrrolidinium surfactants containing a hydroxyethyl fragment (CnPB, n = 12, 14, 16) were prepared for transdermal delivery of non-steroidal anti-inflammatory drugs. In order to obtain the optimal composition, the surfactant/lipid molar ratio (0.02/1; 0.029/1; 0.04/1) and the amphiphile hydrocarbon tail length were varied. Rhodamine B was loaded in all formulations, while meloxicam and ketoprofen in selected ones. For liposomes studied the hydrodynamic diameter was in the range of 80–130 nm, the zeta potential ranged from +35 to +50 mV, EE was 75–99%. Liposome modification leads to a prolonged release of the rhodamine B (up to 10–12 h) and faster release of non-steroidal drugs (up to 7–8 h) in vitro. The ability to cross the skin barrier using Franz cells was investigated for liposomal meloxicam and ketoprofen. The total amount of meloxicam and ketoprofen passed through the Strat-M® membranes during 51 h was 51–114 μg/cm2 and 87–105 μg/cm2 respectively. The evaluation of transdermal diffusion ex vivo showed that total amount of liposomal ketoprofen passed through the skin during 51 h was 140–162 μg/cm2. Liposomes modified with C16PB were found as the most effective inflammation reducing formulation in the carrageenan edema model of rat paw

Introduction of isothiuronium surfactant series: Synthesis, structure-dependent aggregation overview and biological activity

© 2020 Elsevier B.V. For a homologous series of isothiuronium surfactants (S-alkylisothiuronium bromides, CnSU, where n = 10, 12, 14, 16, 18), a synthesis procedure is described and aggregation properties are comprehensively characterized by a variety of techniques. Krafft temperature and critical micelle concentration (cmc) are obtained by methods of conductometry, tensiometry, spectrophotometry, fluorimetry. Using dynamic light scattering and NMR diffusometry, aggregate sizes in aqueous solutions were determined. The aggregation numbers of CnSU systems were estimated by alternative methods. An increase in the length of the alkyl tail from 10 to 16 carbon atoms leads to a decrease in cmc from 16 to 0.5 mM with a decrease in aggregation numbers. S-alkylisothiuronium bromides exhibit solubilization capacity toward a hydrophobic dye Orange OT which is 2–3 times higher than that of alkyltrimethylammonium analogues. Improved solubilization characteristics along with antimicrobial properties manifested at the concentrations of low hemolytic activity allow us to recommend these amphiphiles for the fabrication of soft nanocontainers for hydrophobic guests showing their own biological functionality