Liposomes composition

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. 

Characterizing the resultant complex for the amount of protein per liposome is somewhat more difficult than in other protein conjugation applications. The protein-liposome composition is highly dependent on the size of each liposomal particle, the amount of protein charged to the reaction, and the mole quantity of reactive lipid present in the bilayer construction. An approach to solving this problem is presented by Hutchinson et al. (1989). In analyzing at least 17 different protein-liposome preparations, the ratio of proteindipid content (pg protein/pg lipid) in most of the complexes ranged from a low of about 4 to as much as 675. In some instances, however, up to 6,000 molecules of a particular protein could be incorporated into each liposome. 

Horowitz AT, Barenholz Y, Gabizon AA. In vitro cytotoxicity of liposome-encapsulated doxorubicin dependence on liposome composition and drug release. Biochim Biophys Acta 1992 1109 203-209. 

Schreier, H., P. Moran, and I.W. Caras, Targeting of liposomes to cells expressing CD4 using glycosylphosphatidylinositol-anchored gpl20. Influence of liposome composition on intracellular trafficking. J Biol Chem, 1994. 269(12) 9090-8. 

In the dual liposome-microcapsule system, two factors control the release of the active substance escape from lipsomes into the microcapsule interior, and diffusion across a rate limiting capsule wall into the external environment. This system can take advantage of the inherent instability of some lipsomes while over-coming many of the problems associated with their use by protecting them from the environment by the capsule. At the same time, a new measure of control over the time at which a microcapsule will commence delivery of the enclosed agent is introduced by careful choice of the liposome composition. By changing the nature of the liposomes or of the encapsulant (e.g. alginate) different release times and patterns can be obtained. 

Prepare a 5 mg/ml liposome construction in 20 mM sodium phosphate, 0.15 M NaCl, pH 7.4, containing, on a molar ratio basis, a mixture of PC cholesterol PG other glycolipids of 8 10 1 2. The other glycolipids that can be incorporated include phosphatidyl inositol, lactosylceramide, galactose cerebroside, or various gangliosides. Other liposome compositions may be used, for example, recipes without cholesterol, as long as a periodate-oxidizable component... 

The toxicity of Mn-BOPP is approximately twice that of the unmetallated compound [118]. For this reason liposomal preparations of Mn-BOPP were investigated. The optimal liposome composition was determined and liposomal Mn-BOPP was better tolerated than the free drug in mice. 

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. 

Niemiec, S.M., C. Ramachandran, and N. Weiner. 1995. Influence of nonionic liposomal composition on topical delivery of peptide drugs into pilosebaceous units An in vivo study using the hamster ear model. Pharm Res 12 1184. 

Liposomes used for transfection are either large unilamellar vesicles (LUVs) of 100 to 200 nm in diameter or small unilamellar vesicles (SUVs) of 20 to 100 nm. Liu et al.124 have reported that for a given liposome composition, multilamellar vesicles (MLVs) of 300 to 700 nm in diameter exhibit higher transfection efficiency than SUVs. However, more recent studies on the nature of the liposome-DNA complex (or lipoplex) revealed that lipoplexes from SUVs or MLVs do not differ significantly in size. On the other hand, the composition of the medium, not the type of the liposome used in the preparation of the lipoplex, plays a key role in determining the final size of the complex. And the transfection efficiency is also shown to depend on the final size of the complexes but not the type of the liposome.125... 

In a more recent study, vesicle skin interactions were examined with confo-cal laser scanning microscopy (CLSM) [36], A large number of liposome compositions were examined. These studies revealed that the liposome constituents were only present in the outermost layers of the SC and that the constituents only acted as penetration enhancers, which is in contrast to the studies of Holland et al. Whether these differences in findings are due to another study design or to a difference in vesicle components is not clear. 

S. M. Dowton, Z., Hu, C. Ramachandran, D. F. H. Wallach, and N. Weiner, Influence of liposomal composition on topical delivery of encapsulated cyclosporin A, I. An in vitro study using hairless mouse skin, STP Pharma Sciences 3 404-407 (1993). 

The rate of liposome accumulation in alveolar type-II cells is dependent on lipid composition. It is therefore possible to select liposome compositions displaying minimal interaction with these cells and thereby function as controlled-release systems for entrapped solutes. For example, liposomes composed of dipalmitoylphosphatidylcholine and cholesterol and containing entrapped sodium cromoglycate will provide sustained delivery of the drag for over 24 hours. Conversely other liposome compositions could be utilized for enhanced epithelial interaction and transport of the drug (e g. cationic lipids for the cellular delivery of the CFTR gene). 

Further modifications of the liposomal composition have led to an improved formulation of the cationic liposomes containing raf ASO (md-LErafAON). The md-LErafAON formulation exhibits superior safety and pharmacokinetic profiles and is an effective anti-tumor agent in a human prostate tumor xenograft model. 

Oussoren, C., Eling, W. M., Crommelin, D. J., Storm, G., and Zuidema, J. (1998), The influence of the route of administration and liposome composition on the potential of liposomes to protect tissue against local toxicity of two antitumour drugs, Biochim. Biophys. Acta, 1369,159-172. 

Gabizon, A., Price, D. C., Huberty, I, Bresalier, R. S., and Papahadjopoulos, D. (1990), Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors Biodistribution and imaging studies, Cancer Res., 50, 6371-6378. 

Wasan KM, Brazeau GA, Keyhani A, et al. Roles of liposome composition and temperature in distribution of amphotericin B in serum lipoproteins. Antimicrob Agents Chemother 1993 37 246-50. 

Weigh the required lipid or lipids and Choi (if included in the liposome composition) quantities for the preparation off mL of liposomes and place them in a 50 mL round-bottomed flask 16.5 pmol of lipid (PC) or 12.5 mg is the amount per each milliliter of aqueous phase that results in the highest encapsulation yield for CF (1). 

Buchanan KD, Huang S, Kim H, Macdonald RC, McPherson DD (2008) Echogenic liposome compositions for increased retention of ultrasound reflectivity at physiologic temperature. J Pharm Sci 97 2242-2249... 

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