Interactions of primaquine and chloroquine with PEGylated phosphatidylcholine liposomes

This study aimed to analyze the interaction of primaquine (PQ), chloroquine (CQ), and liposomes to support the design of optimal liposomal delivery for hepatic stage malaria infectious disease. The liposomes were composed of hydrogenated soybean phosphatidylcholine, cholesterol, and distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethyleneglycol]-2000), prepared by thin film method, then evaluated for physicochemical and spectrospic characteristics. The calcein release was further evaluated to determine the effect of drug co-loading on liposomal membrane integrity. The results showed that loading PQ and CQ into liposomes produced changes in the infrared spectra of the diester phosphate and carbonyl ester located in the polar part of the phospholipid, in addition to the alkyl group (CH2) in the nonpolar portion. Moreover, the thermogram revealed the loss of the endothermic peak of liposomes dually loaded with PQ and CQ at 186.6 °C, which is identical to that of the phospholipid. However, no crystallinity changes were detected through powder X-ray diffraction analysis. Moreover, PQ, with either single or dual loading, produced the higher calcein release profiles from the liposomes than that of CQ. The dual loading of PQ and CQ tends to interact with the polar head group of the phosphatidylcholine bilayer membrane resulted in an increase in water permeability of the liposomes.

Multifunctional carriers for controlled drug delivery

In the review we describe a method for concentration of anionic liposomes with encapsulated water-soluble substances within a small volume via electrostatic liposome adsorption on the surface of polymer particles with grafted cationic chains (spherical polycationic brushes), or cationic microgel particles. Dozens of intact liposomes can be bound to each polymer particle, the resulting polymer/liposome complex does not dissociate into the original components in a physiological solution. This allows fabrication of multi-liposomal complexes (MLCs) with a required ratio of encapsulated substances. Two approaches are discussed for the synthesis of stimuli-sensitive MLCs. The first is to incorporate the conformation switch, morpholinocyclohexanol-based lipid, into the liposomal membrane thus forming pH-sensitive liposomes capable of releasing their cargo when acidifying the surrounding solution. These liposomes complexed with the brushes release encapsulated substances much faster than the uncomplexed liposomes. The second is to adsorb liposomes on cationic thermo-responsive microgels. The resulting MLCs contracts upon heating over a volume phase transition temperature from the swollen to the collapsed state of microgel, thus causing the adsorbed liposomes to change drastically their morphology and release an encapsulated substance. Complexation of anionic liposomes with chitosan microgels and polylactide micelles gives MLCs which degrade in the presence of enzymes down to small particles, 10–15 nm in diameter. A novel promising approach suggests that immobilized liposomes can act as a capacious depot for biologically active compounds and ensure their controllable leakage to surrounding solution.

Fusion of Bipolar Tetraether Lipid Membranes Without Enhanced Leakage of Small Molecules

A major challenge in liposomal research is to minimize the leakage of encapsulated cargo from either uncontrolled passive permeability across the liposomal membrane or upon fusion with other membranes. We previously showed that liposomes made from pure Archaea-inspired bipolar tetraether lipids exhibit exceptionally low permeability of encapsulated small molecules due to their capability to form more tightly packed membranes compared to typical monopolar lipids. Here, we demonstrate that liposomes made of synthetic bipolar tetraether lipids can also undergo membrane fusion, which is commonly accompanied by content leakage of liposomes when using typical bilayer-forming lipids. Importantly, we demonstrate calcium-mediated fusion events between liposome made of glycerolmonoalkyl glycerol tetraether lipids with phosphatidic acid headgroups (GMGTPA) occur without liposome content release, which contrasts with liposomes made of bilayer-forming EggPA lipids that displayed ~80% of content release under the same fusogenic conditions. NMR spectroscopy studies of a deuterated analog of GMGTPA lipids reveal the presence of multiple rigid and dynamic conformations, which provide evidence for the possibility of these lipids to form intermediate states typically associated with membrane fusion events. The results support that biomimetic GMGT lipids possess several attractive properties (e.g., low permeability and non-leaky fusion capability) for further development in liposome-based technologies.

Homoeopathic drug induced change in liposomal anisotropy and associated change in van’t Hoff enthalpy

Using liposomal membrane of 1, 2-dipalmitoyl-sn -glycero-3- phosphatidyl choline, a well accepted model for biological membrane, we have measured the change in membrane anisotropy due to incorporation of three homoeopathic drugs silicea, sulphur and calc carb and the associated values of change in Van’t Hoff enthalpy have been calculated. Our experimental results reveal that these three homoeopathic drugs affect the membrane anisotropy in different ways and this change depends upon the potency of the medicine.

Effect of Different Anthocyanidin Glucosides on Lutein Uptake by Caco-2 Cells, and Their Combined Activities on Anti-Oxidation and Anti-Inflammation In Vitro and Ex Vivo

The interactive effects on anti-oxidation and anti-inflammation of lutein combined with each of the six common anthocyanidin glucosides were studied in both chemical and cellular systems. The combined phytochemicals showed an antagonism in the inhibition of lipid oxidation in a liposomal membrane, but showed an additive effect on cellular antioxidant activity in Caco-2 cells. Lutein was an active lipoxygenase inhibitor at 2–12 μM while anthocyanins were inactive. The concentration of lutein when it was used in combination with anthocyanins was 25–54% higher than when lutein was used alone (i.e., IC50 = 1.2 μM) to induce 50% of lipoxygenase inhibition. Only the combination of lutein with malvidin-3-glucoside showed anti-inflammatory synergy in the suppression of interleukin-8, and the synergy was seen at all three ratios tested. Some mixtures, however, showed anti-inflammatory antagonism. The presence of anthocyanins (5–7.5 μM) did not affect lutein uptake (2.5–5 μM) by Caco-2 cells.