Search

The bacteriostatic and/or bactericidal properties of few phosphoramide-based amphiphilic compounds on human pathogenic bacteria were previously reported. In this study, the potential of two cationic (BSV36 and KLN47) and two zwitterionic (3 and 4) amphiphiles as inhibitors of marine bacterial growth and biofilm formation were investigated. Results showed that the four compounds have little impact on the growth of a panel of 18 selected marine bacteria at a concentration of 200 µM, and up to 700 µM for some bacterial strains. Interestingly, cationic lipid BSV36 and zwitterionic lipids 3 and 4 effectively disrupt biofilm formation of Paracoccus sp. 4M6 and Vibrio sp. D02 at 200 µM and to a lesser extent of seven other bacterial strains tested. Moreover, ecotoxicological assays on four species of microalgae highlighted that compounds 3 and 4 have little impact on microalgae growth with EC50 values of 51 µM for the more sensitive species and up to 200 µM for most of the others. Amphiphilic compounds, especially zwitterionic amphiphiles 3 and 4 seem to be promising candidates against biofilm formation by marine bacteria. [ABSTRACT FROM AUTHOR]

The active transport of nanoparticles into the solid tumor through cell transcytosis has shown great promise in cancer nanomedicine, but it is challenging to develop efficient active transporting nanomedicines with the potential for clinical translation. Here, a type of tertiary amine oxide (TAO)‐containing zwitterionic liposomal nanocarriers is developed that can hitchhike red blood cells (RBCs) to tumor blood vessels and enter solid tumors through transcytosis. To boost the active‐transporting capability, a library of the TAO liposomes (TAOLs) with different chemical structures and particle sizes is constructed and screened by their stability and active transporting capability. Two types of TAOLs are identified that can induce efficient tumor cell transcytosis through rapid macropinocytosis and endoplasmic reticulum/Golgi‐involved exocytosis. It is found that these zwitterionic TAOLs can hitchhike RBCs to gain long blood circulation, get off the cell at the tumor site, effectively enter the tumor through transcytosis, and infiltrate the whole tumor. The chemotherapeutic drug‐loaded liposomes can stop the tumor progression of mice bearing human hepatocellular carcinoma HepG2 cells, exhibiting superior antitumor activity compared to the traditional liposomal drug. This study demonstrates a strategy to construct effective active transporting liposomal nanomedicines for efficient tumor entrance. [ABSTRACT FROM AUTHOR]

A lipid named DCPA was synthesized under microwave‐assisted heating. DCPA possesses a pyridine betaine, hydrophilic group that can be complexed with water through hydrogen bonding (DCPA‐H2O). DCPA‐H2O liposomes became protonated relatively fast already at pH<6.8, due to the high HOMO binding energy of DCPA‐H2O. In murine models, DCPA‐H2O liposomes had longer blood circulation times than natural DPPC or cationic DCPM liposomes, while after tail‐vein injection DCPA‐H2O liposomes targeted faster to solid tumors and intra‐abdominal infectious biofilms. Therapeutic efficacy in a murine, infected wound‐healing model of tail‐vein injected ciprofloxacin‐loaded DCPA‐H2O liposomes exceeded the ones of clinically applied ciprofloxacin as well as of ciprofloxacin‐loaded DPPC or DCPM liposomes. [ABSTRACT FROM AUTHOR]

Amyloid beta peptide (AβP) is a natural peptide, normally released into the cerebrospinal fluid (CSF), that plays a key role in Alzheimer's disease. The conversion of the peptide from a native soluble form to a non-native and often insoluble form, such as small and large aggregates, protofibrils and fibrils of AβP appears to be implicated in the pathogenesis of AD. Although the molecular mechanisms of AβP neurotoxicity are not fully understood, a large body of data suggests that the primary target of amyloid peptides is the cell membrane of neurons, that may modulate the structural and functional conversion of AβP into assemblies involved in pathological processes. In our study, we provide a systematic investigation of AβP1-42's ability to incorporate and form channel-like events in membranes of different lipid composition and focus on cholesterol and its oxidation products. We propose that cholesterol and its oxidation products can be considered neuroprotective factors because a) by favouring AβP1-42 insertion into membranes, the fibrillation/clearance balance shifts toward clearance; b) by shifting channel selectivity toward anions, the membrane potential is moved far from the threshold of membrane excitability, thus decreasing the influx of calcium into the cell. [ABSTRACT FROM AUTHOR]

Purpose: We describe a nucleation-based method which allows for the generation of monodisperse lipid nanoparticles over a range of diameters. Using a set of novel zwitterionic lipids and inverse phosphocholine lipids with pKas ranging from 2 to 5, we showed how the hydrodynamic diameter of lipid nanoparticles can be systematically manipulated over a 60 nm to 500 nm size range. Method: Lipid nanoparticles were prepared by adding an anti-solvent, such as water, to the organic phase containing the lipid components. This led to super-saturation and the spontaneous formation of particles. Results: The growth and final particle size was controlled by the ratio of the components in the ternary system: lipid, organic solvent and aqueous phase. Particles with diameter below 125 nm were formed under conditions where the super-saturation coefficient was between 2.3 and 20. PEG-lipid served as an efficient growth inhibitor except at very high and low lipid concentrations. Encapsulation efficiency of siRNA into lipid nanoparticles was shown to be pH-dependent and requires the protonation of the anionic carboxylate groups of the zwitterionic lipids, emphasizing the importance of electrostatic forces. Conclusion: This process enables high encapsulation efficiency of nucleic acids and allows the size of lipid nanoparticles to be controlled. [ABSTRACT FROM AUTHOR]

Abstract: This work is a review of the effect of different monovalent anions (belonging to the Hofmeister series) on a single model amphiphile, phosphatidylcholine molecules in contact with water, in three different geometries, Langmuir monolayers, bilayers and micelles, which differ by area per molecule and radius of curvature. The zwitterionic lipids DPPC (1,2-dipalmitoyl-phosphatidylcholine) and DPC (Dodecylphosphocholine) have been used to form the three geometries. The salt solutions used were NaCl, NaBr, NaNO3, NaI, NaBF4, NaClO4 and NaSCN. Various interfacial and bulk experimental techniques were used in order to study the effect of the anions on the amphiphiles in the three geometries. The interfacial techniques used were surface pressure–area isotherms, Brewster angle microscopy (BAM), Grazing incidence X-ray diffraction (GIXD), infrared reflection absorption spectroscopy (IRRAS). The bulk sensitive techniques used were small-angle X-ray scattering (SAXS), osmotic stress (OS) and light scattering. The experimental results obtained from the three model systems indicate that the interfaces become charged through lipid-ion association. The results were fitted with appropriate theoretical models to provide “binding” or “partitioning” constants of anions in the headgroup region of the lipid molecules. The theoretical analysis strongly suggests that the anions do not associate with the lipid molecules through a local chemical reaction, but rather they partition inside the disordered lipid interfaces. [Copyright &y& Elsevier]

We have studied the effect of acidic pH on the phase behavior of the zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) using differential scanning calorimetry and x-ray scattering. Dispersions of DMPC in HCl solutions of pH = 4 and 3 behave identical to dispersions in water. The main transition temperature increases sharply and the pre-transition disappears at lower pH. An untilted gel phase is observed at pH = 2 and 1, in contrast to the tilted gel phase found at higher pH. The relatively large periodicity of the untilted gel phase, in comparison to that of the tilted gel phase occurring near neutral pH, clearly demonstrates the simultaneous charging and dehydration of the headgroups as the pH approaches the pK of the phosphate group. Headgroup dehydration at low pH also leads to the formation of DMPC crystallites and the inverted hexagonal phase at low and high temperatures, respectively, after a few days of incubation. These results show the significant effect of acidic pH on the phase behavior of zwitterionic lipids. • Phase behavior of phosphatidylcholine lipids altered at low pH. • Main-transition temperature rises sharply and the pre-transition disappears. • Effective headgroup size decreases due to dehydration. • Formation of a gel phase without chain tilt and an inverted hexagonal phase. [ABSTRACT FROM AUTHOR]

A novel "symbiotic self-assembly" strategy that integrates the advantages of biocompatible lipids with a structurally robust polymer to efficiently encapsulate and deliver siRNAs is reported. The assembly process is considered to be symbiotic because none of the assembling components are capable of self-assembly but can form well-defined nanostructures in the presence of others. The conditions of the self-assembly process are simple but have been chosen such that it offers the ability to arrive at a system that is noncationic for mitigating carrier-based cytotoxicity, efficiently encapsulate siRNA to minimize cargo loss, be effectively camouflaged to protect the siRNA from nuclease degradation, and efficiently escape the endosome to cause gene knockdown. The lipid-siRNA-polymer (L-siP) nanoassembly formation and its disassembly in the presence of an intracellular trigger have been extensively characterized experimentally and through computational modeling. The complexes have been evaluated for the delivery of four different siRNA molecules in six different cell lines, where an efficient gene knockdown is demonstrated. The reported generalized strategy has the potential to make an impact on the development of a safe and effective delivery agent for RNAi-mediated gene therapy that holds the promise of targeting several hard-to-cure diseases.