Vesicle permeation

The development of amphipathic fluorescent dyes that label endocytic vesicles has permitted the study of endo-cytosis in nerve terminals in real time [25,26], The probe FM1-43 equilibrates between the aqueous phase and the membrane but is not membrane-permeating. The plasmalemma becomes fluorescent (Fig. 10-8). Upon endocytosis, the labeled membrane is internalized. When removed from the extracellular medium, the dye is retained by the endocytic vesicles but lost from the plasmalemma. Endocytic vesicles are transformed into synaptic vesicles containing FM1-43. Importantly, recycled synaptic vesicles lose the probe upon exocytosis. 

The MARTINI model effectively replaces three to four heavy atoms with a bead, parameterized to reproduce condensed-phase thermodynamic data of small molecules [23]. The MARTINI model has been used to investigate many biological processes, such as lung surfactant collapse [24], nanoparticle permeation in bilayers [25], large domain motion of integral membrane proteins [26], vesicle fusion [27,28], and lateral domain formation in membranes [29]. 

Falten et al. recently reported that phospholipid membrane vesicles can be con-stmcted on a filter scaffold without any organic solvent [57-60]. In this system, the phospholipid vesicle occupies the filter pores to form a permeation barrier. This is more relevant to the cellular membrane than PAMPA membranes with organic solvent. The membrane can be stored up to two weeks without significant change and is stable at pH 2-8. The Fa% predictability was compared with BM-PAMPA, DS-PAMPA, Caco-2 and immobilized liposome chromatography, resulting in promising predictability. 

Halevy R, Rozek A, Kolusheva S, Hancock RE, Jelinek R. Membrane binding and permeation by indolicidin analogs studied by a biomimetic lipid/polydiacetylene vesicle assay. Peptides 2003 24 1753-1761. 

Since permeation does not work for enzymes and other macromolecules, these are often incorporated by physical entrapment during the formation of vesicles, and an example is given in Figures 10.2 and 10.3, which illustrate ADP polycondensation inside vesicles. The enzyme is entrapped during the vesiculation and... 

The permeability of solutes across lipid bilayers is a product of the partition coefficient and the transverse diffusion coefficient [30]. Bilayer polymerization can alter solute diffusion by modifying either or both of these processes. In order to examine the effect of polymerization on bilayer permeability a nonionic solute of moderate permeability, [3H-glucose], was encapsulated in the vesicles prior to polymerization, removed from the exterior after polymerization, and its permeation across the bilayer was measured periodically [31]. Quantitative measurements of the 3H-glucose leakage revealed that the formation of linear polymer chains from methacryloyl lipids reduced the permeability coefficient to 0.3 to 0.5 of that of the unpolymerized lipid vesicles. A larger reduction (two orders of magnitude) was only found when crosslinked polymer networks were formed [31]. 

Substrate entrapment, retainment, and ion permeabilities are important properties of polymerized SUVs. Indeed, substrates entrapped in polymerized SUVs display much lower leakage rates than those encapsulated in non-polymerized SUVs [158-160, 325, 326]. Selective polymerization allows a fine control of acid and base transport from the bulk solution to the vesicle interiors, or vice versa. These species permeate unpolymerized SUVs almost instantaneously. In partially polymerized SUVs, acid and base transfer occurs on the... 

Fig. 42. Preparation of vesicle membranes with asymmetrically or symmetrically bound polyelectrolytes from lipids with polymerizable counterions [340]. GPC = gel permeation chromatography [72]...

Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug... 

Many studies have employed phospholipids as liposomes (vesicles) to transport drugs into and through human skin. However, a few investigations have also employed phospholipids in a nonvesicular form as penetration enhancers. For example, 1% phosphatidylcholine in PG, a concentration at which liposomes would not form, enhanced theophylline penetration through hairless mouse skin [64]. Similarly, indomethacin flux was enhanced through rat skin by the same phospholipid and hydrogenated soybean phospholipids increased diclofenac permeation through rat skin in vivo. 

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. 

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. 

An early study confirmed that occlusion is detrimental to transfersome penetration enhancement ability. The results of this study clearly demonstrated that, under the occlusive conditions, murine skin permeation of fluorescently labeled lipids from transfersomal suspensions and liposomes is comparable [67]. Furthermore, Guo et al. reported that the vesicles failed to transfer detectable quantities of cyclosporin A through the hydrated abdominal mice skin [71],... 

Holland, H.E., et al. 1994. Estradiol permeation from nonionic surfactant vesicles through human stratum corneum in vitro. Pharm Res 11 659. 

Carafa, M., E. Santucci, and G. Lucania. 2002. Lidocaine-loaded non-ionic surfactant vesicles Characterization and in vitro permeation studies. Int J Pharm 231 21. 

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