Liposomal systems

Ubiquinol-10 (or coenzyme Qio see Corongiu et oL, 1993) (0.4-1.0/iM range of concentrations in human plasma) has recently been proposed as a chain-breaking antioxidant (Beyer, 1990) in LDLs as the first line of defence (Stocker et oL, 1991) and in liposomal systems. 

A challenge in designing liposome systems is the assessment of drug release from such systems in vitro. Use of agarose gel matrices has been reported as one approach to evaluate the release kinetics of liposome-encapsulated materials in the presence of biological components [68],... 

Fig. 8 Nanosystems that may function as simultaneous drug delivery and imaging agents for targeting T cells (a) liposomal systems, (b) solid biodegradable nanoparticulates, and (c) macro-molecular dendrimer complexes. PEG polyethylene glycol, Gd-DTPA gadolininum-diethylene triamine penta acetic acid. (Adapted from [48])...

Satue-Gracia MT, Heinonen M and Frankel EN. 1997. Anthocyanins as antioxidants on human low-density lipoprotein and lecithin-liposome systems. J Agric Food Chem 45 3362—3367. 

Principal differences between bulk media water and membrane water partition coefficients are listed in Table 2. These differences are essentially based on the several orders of magnitude difference in surface-to-volume ratio. In the liposomal system, charges built up due to sorption of charged species can be electrically neutralised by counter-ions from the electrolyte (diffuse double... 

Figure 7. Lipophilicity profile of propranolol in liposomes composed of zwitterionic and charged lipids (phosphatidyl ethanolamine (PE), oleic acid (OA), phosphatidyl inositol (PI)). Conditions of measurements are described in [113]. The dotted line indicates the partitioning profile of propranolol in the egg PC liposome system. The bars show the pH-dependent charge profile of propranolol (hatched bars positively charged propranolol) and the lipids in the membrane (black bars negatively charged lipids). Reprinted from [113] Kramer, S. (2001). Liposome/water partitioning , In Pharmacokinetic Optimization in Drug Research, eds. Testa, B. et al. Reproduced by permission of Verlag Helvetica Chimica Acta, Zurich...

Martinez, F. and Gomez, A. (2002). Thermodynamics of partitioning of some sulfonamides in 1-octanol-buffer and liposome systems, J. Phys. Org. Chem., 15, 874-880. 

Over the past 20 years, our laboratory has played a major role in the development of liposomal systems optimized for the delivery of conventional drugs, almost all of which are encapsulated by pH-gradient techniques. Our initial studies led to the development of several liposomal drug delivery systems in which uptake was driven by the citrate method of generating pH gradients (15,21-23,27,54—58). This was followed by the development of new... 

Boman NL, Mayer LD, Cullis PR. Optimization of the retention properties of vincristine in liposomal systems. Biochim Biophys Acta 1993 1152 253. 

In summary, the preformed vesicle approach and detergent dialysis procedure have enabled development of nucleic acid-based therapeutics with clinical utility. Further applications of these liposomal systems with new nucleic acid-based therapeutics such as small interfering RNA for gene silencing are being developed and have demonstrated promising results (28). 

Mayer LD, Tai LCL, Bally MB, et al. Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients. Biochim Biophys Acta 1990 1025 143. 

In order to prove the efficiency of the liposomal system in tumor therapy (administration of the liposomes after tumor induction), seven animals were treated with 2 x 10 B16 tumor cells (injection of a suspension in 200 pL HBSS into tail vein). After four and seven days the formulation [AVE 3 TRP-2 (10 pg TRP-2) and AVE 3 1826 CpG (1.3 pg CpG)] was given into the foot pad of the hind legs of the mice intradermally. Twenty-one days after the injection of the tumor cells, the animals were sacrificed and the metastases in the prepared lungs were counted. A second group of seven animals received the tumor cells, but no liposomal treatment was applied. Table 2 indicates the high antitumor potency of the formulation. 

The relative concentration of gadolinium can be significantly increased as compared to that achievable with liposomes because the physical stability of the mixed micelles is reached for relatively low amounts of additional lipids and surfactants. It is also worth mentioning that the gadolinium-heads of the complexes embedded in micelles are all exposed to the aqueous phase and can interact directly with the water molecules of the bulk, a situation which is usually not met with liposome systems. 

Liao, K. and Yin, M., Individual and combined antioxidant effects of seven phenolic agents in human erythrocyte membrane ghosts and phosphatidylcholine liposome systems importance of the partition coefficient, J. Agric. Food Chem., 48, 2266, 2000. 

Arora A, Nair NG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch. Biochem. Biophys. 356, 133-141, 1998. 

The fact that, working with these liposome systems, new things are always being discovered, is pleasant, but it also reveals how little we know about their thermodynamic and kinetic properties. It would have been impossible to predict the... 

Another complex biochemical reaction is the polymerase chain reaction (PCR). It has also be implemented in liposomes (Oberholzer et al, 1995a). This reachon was interesting from the point of view of vesicle chemistry because the liposomal system had to endure the extreme PCR condihons, with several temperature cycles up to 90 °C (liposomes were practically unchanged at the end of the reaction) and furthermore, nine different chemicals had to be encapsulated in an individual liposome for the reaction to occur. This was carried out by mechanical entrapment from a solution that contained all components only a minimal number of the in situ formed vesicles could entrap all nine components. These odds notwithstanding, there was a significant synthesis. ... 

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