Vesicular systems

A novel polymerized vesicular system for controlled release, which contains a cyclic a-alkoxyacrylate as the polymerizable group on the amphiphilic structure, has been developed. These lipids can be easily polymerized through a free radical process. It has been shown that polymerization improves the stabilities of the synthetic vesicles. In the aqueous system the cyclic acrylate group, which connects the polymerized chain and the amphiphilic structure, can be slowly hydrolyzed to separate the polymer chain and the vesicular system and generate a water-soluble biodegradable polymer. Furthermore, in order to retain the fluidity and to prepare the polymerized vesicles directly from prev lymerized lipids, a hydrophilic spacer has been introduced. 

The UV absorption of the aqueous vesicular systems, which provides information on the relative concentration of lipids in aqueous system, also proved the enhanced stability of the polymerized vesicles. The absorptions at 238 nm of the unpolymerized vesicles showed a sharp decrease, as seen in Figure 5, as a result of the precipitation of the lipid in the system. However, the absorptions at the same wavelength of the polymerized system showed a relatively steady trend that meant the polymerized lipid had a longer suspension life in the aqueous system. 

In the study of polymerizations of the first vesicular system it has been learned that thermal polymerization in an aqueous medium was not possible because of the hydrolysis of the acetal group. UV irradiation seemed the only practical initial way to perform the polymerization. However, it is difficult to follow and manipulate the polymerization, and therefore it is not possible to control the molecular weight of the polymer chain in the vesicular system. 

The hydrolysis of the cyclic acetal, which was used as the connecting group between the polymer chain and the lipid, was confirmed both by the IR and the proton NMR spectra of the lipid recovered from the vesicular system after standing for 3 weeks at room temperature. The lactone absorption at 1805 cm-1 disappeared from the IR spectrum (Figure 6) as the result of hydrolysis. Furthermore, a new aldehyde absorption band at 1705 cm 1 was observed in the spectrum, which is related to the substituted benzaldehyde group of the hydrolyzed product. The proton NMR spectrum (Figure 10) also clearly showed the formation of the benzaldehyde, as indicated by the peak at 810.20 ppm. 

E.I. Iwuoha, S. Joseph, Z. Zhang, M.R. Smyth, U. Fuhr, and P.R. Ortiz de Montellano, Drug metabolism biosensors electrochemical reactivities of cytochrome CYP101 immobilised in synthetic vesicular systems. J. Pharm. Biom. Anal. 17, 1101-1110 (1998). 

At the point where amphiphiles were recruited to provide the precursors to cell membranes, stable lipid vesicles could have evolved [141] to enclose autocatalytic chiral hypercycles. Credible models for the subsequent evolution of vesicles containing self-replicating chiral molecules have appeared in the literature. [193,194] These vesicles could then emerge from the feldspar spaces [134,192] as micron-sized self-reproducing, energy-metabolizing vesicular systems protobacteria ready to face the hydrothermal world on their own terms. 

Besides differential scanning calorimetry, electron microscopy can also serve for characterizing the mixing behavior of multicomponent vesicular systems. The ripple structure of phospholipids with saturated alkyl chains (also referred to as smectic Bca phase, Fig. 35) is taken to indicate patch formation (immiscibility) in mixed phos-close enough (1-2 nm) lipid molecules are able to diffuse from one membrane to the between the pre- and main-transition of the corresponding phospholipid, electron... 

Blankschtein, D., A. Shiloach, and N. Zoeller. 1997. Thermodynamic theories of micellar and vesicular systems. Curr. Opin. Coll. Interface Sci2 294-300. 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

The first communication about the Chl-sensitized water oxidation to 02 on the outer vesicle interface conjugated with Fe(CN)g reduction at the inner interface appeared in 1977 [42] (see System 2 in Table 1). However an attempt to reproduce this result was a failure [273]. Thus the possibility of water photooxidation in vesicular systems which contain either only Chi molecules or Chi molecules in combination with other photosynthetic pigments is still under discussion. However, embedding of the intact fragments of thylakoids in the vesicle membranes was found to provide the evolution of 02 from water upon illumination [273], But again this process was not conjugated with PET across the membranes. 

Perhaps more important than all these considerations was the fact that preparation of functional vesicular systems led to purification studies and reconstitution of transporters using artificial liposomes and imposed ion gradients to drive translocation. Vesicle systems also bypassed the need to measure binding as the one means... 

Murakami et al. also found that the transamination reaction between hydrophobic pyridoxals (36 and 37) and a-amino acids, to produce a-keto acids, was extremely slow for neutral pyridoxals even in the presence of Cu(n) ions [24]. Detailed kinetic analysis of the reactions carried out in the vesicular system indicated that the transformation of the Cu(n) -quinonoid chelate into the Cu(n) -ketimine chelate was kinetically unfavorable compared with the competing formation of the Cu(n)-aldimine chelate from the same quinonoid species. This problem was solved to a certain extent by quaternization of the pyridyl nitrogen in pyridoxal, as Murakami et al. successfully accomplished transamination between catalyst 36 and L-phenylalanine to produce phenylpyruvic acid. 

Having successfully accelerated the reversible isomerization between the aldimine and ketimine Schiff bases, Murakami et al. then studied how to obtain turnovers in the full transamination reaction between one amino acid and one keto acid [25]. They found that the bilayer vesicle system constituted with 33, 36, and Cu(n) ions showed some turnovers for the transamination between L-phenylalanine and pyruvic add. However, such turnover behavior was not observed in a vesicular system composed of 32, 36, and Cu(n) ions, and an aqueous system involving N-methylpyridoxal and Cu(n) ions without amphiphiles. Therefore, both the hydrophobic effect and the imidazole catalysis effect were proposed as important for the turnover behavior. 

Murakami et al. also found that, for the (3-replacement reaction carried out in the 33-36 vesicular system, L-serine and its hydrophobic benzyl ester derivative show com-... 

Uchegbu, I. F. (2000), Synthetic surfactant vesicles Niosomes and other nonphospholipid vesicular systems, in Drug Targeting and Delivery, Vol. 11, Harwood Academic, Amsterdam. 

As already mentioned, to rationalize the shape and size of the aggregate is difficult and also the number of studies on the relationship between structure and the physicochemical properties of these luminescent metalloaggregates remain limited so far (50,104,114,115), and mostly dealing with spherical micelles, even though few vesicular systems have been also reported (116). In addition, these aggregates have been studied mainly in aqueous solutions, while there are only few known metallosurfactants which aggregate in organic solvents (116,117). 

The ATP-P exchange reaction has been very useful in demonstrating the activity of the complete ATP synthase (CFy-CFi) complex, since it requires an intact system properly incorporated within a vesicular system [39]. Thus, isolated CFi or CFo-CFi, though possessing ATPase activity, do not show ATP-Pj exchange until properly incorporated into a liposomal system. 

Liposomal systems also can form an effective drug reservoir in the upper layers of the skin. This is particularly useful for local skin therapy. Ethosomal carriers composed of phospholipid vesicular systems with alcohols are also effective at enhancing tran -dermal delivery of both lipophilic and hydrophilic compounds. The use of these ethosomes has been used in the delivery of minoxidil to the pilo-sebaceous section of the skin with better results than conventional liposomes. Similar results are reported in clinical studies with acyclovir in a topical therapy treatment of recurrent herpes labialis. Other application reports with ethosomes are patches containing testosterone (37). 

Hunter CA, Dolan TF, Coombs GH, et al. Vesicular systems (niosomes and liposomes) for delivery of sodium stibogluconate in experimental murine visceral leishmaniasis. J Pharm Pharmacol 1988 40 161-165. 

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