Liposome matrix

Masters and Domb [250] reported on an injectable drug delivery system that uses liposomes [251] to release the local anesthetic, bupivacaine, from a liposomal matrix that is both biodegradable and biocompatible to produce SLAB. Bupivacaine due to its minimum vasodilating properties was preferred to other local anesthetics (e.g., lidocaine) allowing the released drug to remain at the site of injection longer [252]. Lipospheres are an aqueous microdispersion of water insoluble, spherical microparticles (0.2 to 100 pm in diameter), each consisting... 

A large variety of drug delivery systems are described in the literature, such as liposomes (Torchilin, 2006), micro and nanoparticles (Kumar, 2000), polymeric micelles (Torchilin, 2006), nanocrystals (Muller et al., 2011), among others. Microparticles are usually classified as microcapsules or microspheres (Figure 8). Microspheres are matrix spherical microparticles where the drug may be located on the surface or dissolved into the matrix. Microcapsules are characterized as spherical particles more than Ipm containing a core substance (aqueous or lipid), normally lipid, and are used to deliver poor soluble molecules... 

FIG. 18 Schematic drawing of a liposome with entrapped functional molecules, coated with an S-layer lattice, that can be used as immobilization matrix for functional molecules. Alternatively, liposomes can be coated with genetically modified S-layer subunits incorporating functional domains. (Modified from Ref. 59.) (b) Electron micrograph of a freeze-etched preparation of an S-layer-coated liposome (bar, 100 nm). 

The binding of carotenoids within the lipid membranes has two important aspects the incorporation rate into the lipid phase and the carotenoid-lipid miscibility or rather pigment solubility in the lipid matrix. The actual incorporation rates of carotenoids into model lipid membranes depend on several factors, such as, the kind of lipid used to form the membranes, the identity of the carotenoid to be incorporated, initial carotenoid concentration, temperature of the experiment, and to a lesser extent, the technique applied to form model lipid membranes (planar lipid bilayers, liposomes obtained by vortexing, sonication, or extrusion, etc.). For example, the presence of 5 mol% of carotenoid with respect to DPPC, during the formation of multilamellar liposomes, resulted in incorporation of only 72% of the pigment, in the case of zeaxanthin, and 52% in the case of (1-carotene (Socaciu et al., 2000). A decrease in the fluidity of the liposome membranes, by addition of other... 

Tumor tissues overexpress matrix metalloproteinases (MMPs). A liposomal pDNA carrier (MEND) was developed containing PEG conjugated to lipid via a peptide linker that is a target sequence for MMPs. In this strategy, PEG is removed from the carrier via MMP-triggered cleavage [198]. Intravenous administration in... 

In contrast to the extensive exploitation of the trapped aqueous volume of the liposomes that serves as nanocontainer for water-soluble molecules, the phospholipid bilayer has not been given the same attention for its use as carrier matrix for lipophilic drugs. An exploratory survey of the number of cited literature references in Medline performed in February 2005 gave the following result. With the general keywords drug and... 

Figure 5 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvance on cytotoxic T-cell (CTL) induction. PBMC from a healthy donor were cultured in the presence of influenza matrix (IM)58 66 (A), IMss-eo and control liposomes (B) or IMss-ee and IRIV (C). After a seven-day culture, percentages of IMss-ee speciflc CTL within cultured cells were quantifled by HLA-A0201/IM58 gfi phosphatidylethanolamine tetramer staining (fluorescence 2) and anti CDS fluorescein isothiocyanate staining (fluorescence 1). CTL precursor frequencies detected in IMss-ee and IRIV stimulated cultures within the same experiment are shown in (D). Source From Ref 6.

Lipid nanodispersions (SLN and NLC) are complex, thermodynamically unstable systems. The colloidal size of the particles alters physical features (e.g., increasing solubihty and the tendency to form supercooled melts). The complex structured lipid matrix may include hquid phases and various lipid modifications that differ in the capacity to incorporate drugs. Lipid molecules of variant modifications may differ in their mobility. Moreover, the high amount of emulsifier used may result in liposome or micelle formation in addition to the nanoparticles. 

Much research has gone into raising the sensitivity and selectivity of immunosensors to the desired levels. Several labels have proved to ensure a high sensitivity, yet radioisotopic labels have essentially been avoided. Non-isotopic labels for immunosensors include various enzymes, catalysts, fluorophores, electrochemically active molecules and liposomes. Labelled immunosensors are basically designed so that immunochemical complexation takes place on the surface of the sensor matrix. There are several variants of the procedure used to form an immunocomplex on the matrix. In the final step, however, the label should always be incorporated into the immunocomplex for determination, as shown in Fig. 3.27.B. 

Figure 10.20 (a) Matrix effect for oleate addition to pre-formed POPC liposomes. In this case, mixed oleate/POPC vesicles are finally formed. Note the extraordinary similarity between the size distribution of the pre-formed liposomes and the final mixed ones. By contrast, the size distribution of the control (no pre-existing liposomes) is very broad, (i) Sodium oleate added to POPC liposomes, radius = 44.13, P-index = 0.06 (ii) POPC liposomes, radius = 49.63, P-index = 0.05 (iii) sodium oleate in buffer, radius = 199.43, P-index = 0.26. (b) matrix effect for the addition of fresh oleate to pre-existing extruded oleate vesicles. In this case, the average radius of the final vesicles is c. 10% greater than the pre-added ones, and again the difference with respect to the control experiment (no pre-added extruded vesicles) is striking, (i) Oleate vesicles extruded 100 nm, radius = 59.77, P-index = 0.06 (ii) oleate added to oleate vesicles, extended 100 nm, radius = 64.82, P-index 0.09 (iii) sodium oleate in buffer, radius = 285.88, P-index = 0.260. (Modified from Rasi et al, 2003.)... 

In addition to enzymatic hydrolysis of natural lipids in polymeric membranes as discussed in chapter 4.2.2., other methods have been applied to trigger the release of vesicle-entrapped compounds as depicted in Fig. 37. Based on the investigations of phase-separated and only partially polymerized mixed liposomes 101, methods to uncork polymeric vesicles have been developed. One specific approach makes use of cleavable lipids such as the cystine derivative (63). From this fluorocarbon lipid mixed liposomes with the polymerizable dienoic acid-containing sulfolipid (58) were prepared in a molar ratio of 1 9 101115>. After polymerization of the matrix forming sulfolipids, stable spherically shaped vesicles are obtained as demonstrated in Fig. 54 by scanning electron microscopy 114>. 

Four methods have been developed for enzyme immobilization (1) physical adsorption onto an inert, insoluble, solid support such as a polymer (2) chemical covalent attachment to an insoluble polymeric support (3) encapsulation within a membranous microsphere such as a liposome and (4) entrapment within a gel matrix. The choice of immobilization method is dependent on several factors, including the enzyme used, the process to be carried out, and the reaction conditions. In this experiment, an enzyme, horseradish peroxidase (donor H202 oxidoreductase EC 1.11.1.7), will be imprisoned within a polyacrylamide gel matrix. This method of entrapment has been chosen because it is rapid, inexpensive, and allows kinetic characterization of the immobilized enzyme. Immobilized peroxidase catalyzes a reaction that has commercial potential and interest, the reductive cleavage of hydrogen peroxide, H202, by an electron donor, AH2 ... 

Similar to hydrophilic flavonoids, hydrophobic flavonoids can affect membrane permeability. Alterations in this biophysical property of liposome bilayers lead to the release of bulky molecules entrapped into the inner aqueous space. As mentioned in the previous section, a strong correlation was found between flavonoid retention to a hydrophobic matrix and their capacity to induce membrane leakage [Ollila et al., 2002]. Interestingly, hydrophilic flavonoids, such as (—)-epicatechin and related procyanidins (dimer to hex-amer) prevented Fe2 + -mediated liposome permeabilization, although in this case the beneficial effect could be related to both their antioxidant and metal chelating capacities and their membrane stabilizing properties [Verstraeten et al., 2004],... 

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