Lipid membranes are extremely stable envelopes allowing cells to survive in various environments and to maintain desired internal composition. Membrane permeation through formation of transversal pores requires substantial external stress. Practically, pores are usually formed by application of lateral tension or transmembrane voltage. Using the same approach as was used for obtaining continuous trajectory of pore formation in the stress-less membrane in the previous article, we now consider the process of pore formation under the external stress. The waiting time to pore formation proved a non-monotonous function of the lateral tension, dropping from infinity at zero tension to a minimum at the tension of several millinewtons per meter. Transmembrane voltage, on the contrary, caused the waiting time to decrease monotonously. Analysis of pore formation trajectories for several lipid species with different spontaneous curvatures and elastic moduli under various external conditions provided instrumental insights into the mechanisms underlying some experimentally observed phenomena.
A vesicle is a microscopic particle composed of a lipid bilayer membrane that separates the inner aqueous compartment from the outer aqueous environment. Palmitoleate-palmitoleic acid vesicles were prepared and their physico-chemical properties were investigated. Moreover, mixed vesicles composed of palmitoleic acid and PEGylated lipid and/or a mixture of phospholipids were also prepared. The stabilizing effects of these double-chain lipids on the formation of palmitoleate-palmitoleic acid vesicles were studied. Stability of the vesicle suspension was examined using particle size and zeta potential at 30 °C. The magnitude of the zeta potential was relatively lower in the vesicle suspension with the presence of phospholipid. Although some of the mixed vesicles that were formed were not very stable, they displayed potential for encapsulating the active ingredient calcein and the encapsulation efficiencies of calcein were encouraging. The palmitoleate-palmitoleic acid-DPPE-PEG2000 vesicle showed the most promising stability and encapsulation efficiency.
Analysis of 300 ns (ns) molecular dynamics (MD) simulations of an adenosine A2a receptor (A2a AR) model, conducted in triplicate, in 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) bilayers reveals significantly different protein dynamical behavior. Principal component analysis (PCA) shows that the dissimilarities stem from interhelical rather than intrahelical motions. The difference in the hydrophobic thicknesses of these simulated lipid bilayers is potentially a significant reason for the observed difference in results. The distinct lipid headgroups might also lead to different molecular interactions and hence different protein loop motions. Overall, the A2a AR shows higher mobility and flexibility in POPC as compared to POPE.
In this work, we studied whether chondroitin sulfates and dextran sulfates (DXSs) can influence hypochlorite-induced peroxidation of phosphatidylcholine (PC) liposomes. Multilamellar liposomes (2 mg lipid/ml) were prepared in phosphate buffer, pH 7.4, with NaCl or not and exposed to reagent HOCl/ClO- (1mM) at 37 degrees C in the presence of different concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), DXS 8000, DXS 40,000, and DXS 500,000. Lipid peroxidation was assessed by thiobarbituric acid-reactive substance (TBARS) production. DXSs and C6S enhanced TBARS production in a dose-dependent manner. The decline in TBARS production at the relatively high C6S concentrations may be attributed to C4S present in C6S, since in contrast to C6S, C4S is known to react with hypochlorite. Dextrans, nonsulfated analogues of DXS, failed to modulate TBARS production. This fact indicates the important role of negatively charged sulfate groups for DXS to facilitate hypochlorite-induced peroxidation of PC liposomes. The electrostatic nature of the mechanism providing for the pro-oxidative effect of DXS was also supported by the influence of liposome surface charge and solution ionic strength on the extent of liposome peroxidation. The addition of calcium ions to the incubation mixture did not prevent the pro-oxidative action of DXS. The relevance of the results to atherogenesis is discussed.
Highly ordered ring-like structures are formed via the directed assembly of lipid domains in supported bilayers, using the extracellular matrix protein fibronectin. The ability of biological molecules to guide nanoscale assembly suggests potential biomimetic approaches to nanoscale structures.
A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.
Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 μm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (-26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1max) and 24 ± 0.06 h (T2max). These peaks corresponded to peak plasma concentrations (C1max and C2max) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t1/2, el) and the elimination rate constant (Kel). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.