Membrane encapsulation, cholesterol

Cholesterol oxidation product evaluation has continued. However, a myriad of problems have plagued these investigations including insufficient survival time among experimental animals, spontaneous occurrence of fibrosarcoma and membrane encapsulation (oleotua) of injected material, probably due to physical (surface or texture) effects (62-65). Frequently studies were complicated by the use of an oily vehicle, as discussed previously for sesame... 

The use of the reverse phase evaporation method permits inclusion of 50 and more percent of the substance to be encapsulated from the water phase into the liposomes. Besides, a variety of methods have been developed to obtain lyophilized liposomal preparations possessing good storage stability. The in vitro release rate of different compounds from liposomes, including proteins of moderate molecular weight, is usually under 1% per hour, assuming that the incubation temperature sufficiently differs from the phase transition temperature of a given phospholipid, since the maximal permeability of liposomes is usually observed at temperatures close to the phase transition temperature of the liposomal phospholipid. In vivo, this parameter can vary within wide limits from minutes to hours and depends on the liposome membrane composition, cholesterol content, and disposition within the body. 

Li, L., Braiteh, F.S., and Kurzrock, R., Liposome-encapsulated curcumin in vitro and in vivo effects on proliferation, Apopf. Signal. Angiogen. Cancer, 104, 1322, 2005. Socaciu, C., Jessel, R., and Diehl, H.A., Competitive carotenoid and cholesterol incorporation into liposomes effects on membrane phase transition, fluidity, polarity... 

Probucol, another di-r-butyl phenol, is an anti-atherosclerotic agent that can suppress the oxidation of low-density lipoprotein (LDL) in addition to lowering cholesterol levels. The antioxidant activity of probucol was measured, using EPR, with oxidation of methyl linoleate that was encapsulated in liposomal membranes or dissolved in hexane. Probucol suppressed ffee-radical-mediated oxidation. Its antioxidant activity was 17-fold less than that of tocopherol. This difference was less in liposomes than in hexane solution. Probucol suppressed the oxidation of LDL as efficiently as tocopherol. This work implies that physical factors as well as chemical reactivity are important in determining overall lipid peroxidation inhibition activity (Gotoh et al., 1992). 

Liposomes made from pure phosphatidylcholine or containing lipids that are found in the cell membrane complex of wool (e.g. cholesterol) have been used to encapsulate aqueous chlorine solutions in chlorination processes [61,62]. The results showed improvements in... 

The correct ratio of lipid constituents is important to form stable liposomes. For instance, a reliable liposomal composition for encapsulating aqueous substances may contain molar ratios of lecithin cholesterol negatively charged phospholipid (e.g., phosphatidyl glycerol (PG)) of 0.9 1 0.1. A composition that is typical when an activated phosphatidylethanolamine (PE) derivative is included may contain molar ratios of phosphatidylcholine (PC) cholesterol PG derivatized PE of 8 10 1 1. Another typical composition using a maleimide derivative of PE without PG is PC male-imide-PE cholesterol of 85 15 50 (Friede et al., 1993). In general, to maintain membrane stability, the PE derivative should not exceed a concentration ratio of about l-10mol PE per lOOmol of total lipid. 

Fig. 1 Schematic illustration of a liposome encapsulating a hydrophilic drug. The membrane contains phospholipid and cholesterol molecules. (Reprinted with permission from Ref. 3 with slight modification. Copyright 1998 Adis International.)... 

More recently, Carafa et al. showed that niosomes could be obtained from polyoxyethylene sorbitan monolaurate-cholesterol in aqueous environment. These authors investigated the delivery of lidocaine HC1 and lidocaine base from vesicles through silicone membrane and nude mice skin [44]. It was found that only the charged molecule (loading pH 5.5) could be encapsulated within the vesicles ( 30%). This behavior was explained by the entrapment ability of the hydrophilic moiety within the aqueous core of the vesicles. The lipophilic unionized form of lidocaine (loading pH 8.6) remained unattached. The amount of lidocaine permeated through nude mice skin from these niosomes was similar to liposomes and only about twofold greater than from a micellar system. 

The stability of various niosomal formulations depends on factors such as preparation methods, storage temperature, the encapsulated drug, the surfactants, and additive mixture [41,52,64,65], It may be possible to stabilize niosomes by a variety of methods such as the use of membrane-spanning lipids, the interfacial polymerization of surfactant monomers in situ, addition of polymerized surfactants, cholesterol, steric and electrostatic stabilizers to the formulation [41,52]. In general, vesicle aggregation may be prevented by inclusion of... 

Cholesterol and a-tocopherol are used quite often to increase the rigidity and stability of liposomal membranes [88,106-108]. In most cases cholesterol appears to improve the encapsulation of both hydrophilic and hydrophobic compounds. However, if the drug is lipophilic and partitions in the liposome membrane, there is a good chance that it might be displaced by adding increasing amounts of cholesterol in the bilayer (as observed in the case of dexamethasone encapsulating liposomes in our laboratory). 

The rote of cholesterol in the fluidity of biological membranes is characterized as essential. Cholesterol is a silent molecule and in the case of lipid bilayers and liposomes it is included into bilayers to control the rate of the release of encapsulated molecules or to influence the stability of liposomes. The addition of cholesterol in lipid bilayers composed of DPPC, at concentrations more than 20%, results in the decrease of the Tin and elimination of the pretransition temperature. 

DepoCyt (Pacira Pharmaceuticals, San Diego, CA) is a slow release liposome-encapsulated cytarabine formulation, recently approved for intrathecal administration in the treatment of neoplastic meningitis and lymphomatous meningitis (30-32). The Depo-Foam platform used in DepoCyt , is essentially a spherical 20-pm multi-lamellar matrix comprised of phospholipids/ lipid mixture, similar to normal human cell membranes (phospholipids, triglycerides and cholesterol) (33). 

We selected Pseudomonas pictorum (ATCC 23328) as another model system because it can degrade cholesterol. The standard encapsulation method does not result in a high-porosity membrane that would allow lipoprotein-cholesterol to cross. Therefore, we devised a modified method to prepare high-porosity agar microspheres. There was no evidence of leakage of the enclosed bacteria. Open pore agar beads were incubated in serum, and the bacterial action did not significantly... 

---