Dipalmitoylphosphatidylcholine-cholesterol

Muramatsu, K., et al. 1994. Effect of soybean-derived sterol and its glucoside mixtures on the stability of dipalmitoyl-phosphatidylcholine and dipalmitoylphosphatidylcholine/cholesterol liposomes. Int J Pharm 107 1. 

Ten years later, Taylor et al. [84] published a study on the effects of Upo-some encapsulation on the pharmacokinetics in humans of sodium cromoglycate, a water-soluble antiasthmatic/antiallergenic compound. The dmg was formulated in dipalmitoylphosphatidylcholine/cholesterol (DPPC/CH) (1 1 molar ratio) liposomes and administered as a nebulized aerosol. The researchers demonstrated that, compared with drug administered in solution, the liposomally encapsulated dmg achieved a lower C ax and prolonged plasma half-life, indicating that the liposomes were controlling dmg delivery. 

Tu, K., Klein, M. L. and Tobias, D. J. (1998). Constant-pressure molecular dynamics investigation of cholesterol effects in a dipalmitoylphosphatidylcholine... 

Fig. 11. Evidence that a membrane-associated immunochemical reaction (complement fixation) depends on the mobility of the target hapten (IX) in the plane of a model membrane. The extent of the immunochemical reaction, complement fixation, is measured by A Absorbance at 413 nm. Temperature is always 32°C, which is above the chainmelting temperature (23°C) of dimyristoylphosphatidylcholine used for the data given in A and below the chain-melting transition temperature (42°C) of dipalmitoylphosphatidyl-choline used for the data in B. Thus A refers to a fluid membrane and B refers to a solid membrane. The numbers by each curve are equal to c, the mole % of spin-label hapten IX in the plane of the lipid membrane. It will be seen that complement fixation, as measured by A Absorbance at 413 nm is far more effective in the fluid membrane than in the solid membrane at low hapten concentrations (i.e., c 0.3 mo e%). In C the lipid membrane host is a 50 50 mole ratio mixture of cholesterol and dipalmitoylphosphatidylcholine. The immunochemical data suggest that this membrane is in a state of intermediate fluidity. Specific affinity-purified IgG molecules were used in these experiments. (For further details, see Ref. 5.)... 

Liposomes were formed from 1,2-dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Choi) and the effect of liposomal entrapment on pulmonary absorption of insulin was related to oligomerization of insulin (Liu et al. 1993). Instillation of both dimeric and hexameric insulin produced equivalent duration of hypoglycemic response. However, the initial response from the hexameric form was slightly slower than that from dimeric insulin, probably due to lower permeability across alveolar epithelium of the hexameric form caused by larger molecular size. The intratracheal administration of liposomal insulin enhanced pulmonary absorption and resulted in an absolute bioavailability of 30.3%. Nevertheless, a similar extent of absorption and hypoglycemic effects was obtained from a physical mixture of insulin and blank liposomes and from liposomal insulin. This suggests a specific interaction of the phospholipid with the surfactant layer or even with the alveolar membrane. 

F. Muller-Landau and D.A. Cadenhead, Molecular packing in steroid-lecithin monolayers, Part I, Pure films of cholesterol, 3-doxyl-cholestane, 3-doxyl-17-hydroxyl-androstane, tetradecanoic acid and dipalmitoylphosphatidylcholine, Chem. Phys. Lipids 25 (1979)299-314. 

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). 

The two major components of biological membranes are lipids and cholesterol. One major class of lipids are the phospholipids. The H spectrum of one such phospholipid, dipalmitoylphosphatidylcholine (DPPC), in chloroform is shown in Figure 14.28. The H spectrum of cholesterol in chloroform is shown in Figure 14.29 (page 272). 

Pulmonary surfactant is a complex of lipids and proteins with unique surface active properties that is synthesized exclusively in alveolar type II cells. The composition of surfactant is 90% lipids and 5-10% surfactant-specific proteins. The lipid component is made up of dipalmitoylphosphatidylcholine (also called lecithin, 70-80%) and another major phospholipid, phosphatidyl-glycerol (PG, 10%). The remainder of the phospholipids of surfactant are phosphatidylinositol (PI), phos-phatidylethanolamine (PE), and phosphatidylserine (PS). Immature surfactant contains higher amounts of PI compared to PG. Thus, a low ratio of PG to PI indicates lung immaturity. Cholesterol, a neutral lipid, is also a constituent of the lipid component of surfactant. 

Vist, M. and Davis, J. Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures 2H nuclear magnetic resonance and differential scanning calorimetry. Biochemistry, 29, 451,1990. 

Abbreviations CHO, cholesterol DPPC, dipalmitoylphosphatidylcholine FITC, fluorescein isothiocyanate GAS, gas antisolvent POPC,... 

S. Mabrey, P. L. Mateo, and J. M. Sturtevant, High Sensitivity Scanning Calorimetric Study of Mixtures of Cholesterol with Dimyristoyl- and Dipalmitoylphosphatidylcholine, Biochemistry 17, 2464-2468 (1978). 

Figure 9.9 Temperature dependence of the maximum wavenumber of the CH2 asymmetric stretching vibrations in (a) dipalmitoylphosphatidylcholine (DPPC)-chol-esterol and (b) dimyristoylphosphatidylcholine (DMPC)-cholesterol at the molar ratios indicated. The temperature dependence for pure lipids (filled circles) is also given (CoTtijo et al., 1982).

A differential scanning calorimetric study (unpublished) shows that ASG eliminates the phase transition of dipalmitoylphosphatidylcholine (DPPC) just as well, and at the same molar proportion, as cholesterol. SG affects the phase transition by broadening rather than eliminating it. 

Figure 13 Dipalmitoylphosphatidylcholine liposomes undergo a phase transition at 41 -42°C (curve b). This transition is characterized by a pretransition (region 1 in curve b) and a main transition (region 2 in curve b) and has been shown to be a solid gel-to-Uquid crystalline transition of the membrane phospholipids. This phase transition is abolished when cholesterol is incorporated in the membranes at 45 mol% (curve a). Cholesterol increases the order of membranes in the hquid crystalline phase and decrease the order of membranes in the solid gel phase. (Adapted from Ref. 3.)... 

The quantitative determination of phospholipid acyl chain conformational disorder in hydrated systems of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamlne (DPPE), mixtures containing DPPC and cholesterol, and mixtures of DPPC and Gramicidin D has been made using FT-IR. The... 

Tm refers to the gel to liquid crystalline phase transition. DAPC diarachidonoylphosphatidylchohne DGDG digalactosyldiglyceride DLPC dilauroylphosphatidylchohne DMPC dimyristoylphosphatidylcholine Ch cholesterol DPPC dipalmitoylphosphatidylcholine DOPC dioleoylphosphatidylchoUne, and egg PC. 

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