Dipalmitoylphosphatidylcholine liposomes

The half-height width (HHW) of the transition peak is used as a measure of the interactions between solubilized compounds and the phospholipid bilayers [130,133]. This is one of the few available methods for determining the amount of hydrophobic material incorporated into the liposomes. Fildes and Oliver [131] used this criterion to maximize the incorporation of hydrocortisone-21-palmitate in dipalmitoylphosphatidylcholine liposomes. The temperature of the main phase transition was considered independent of steroid content, although the HHW increased to a maximum of 9 at 13.2% before diminishing, indicating the maximum... 

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.)... 

Jizomoto and Hirano [3.41 ] tried to increase the amount of drug inclusions in liposomes by inserting Ca2+ ions in dipalmitoylphosphatidylcholine (DPPC) liposomes. The included volume (mL) per g of liposomes is called Vcap, and this can be increased as a function of the Ca2+ concentration up to ten fold of the minimum Vcap The increase in Vcap is attributed to the electrostatic repulsion between the Ca ions, which reduces the number of lamella and increases the diameter of the liposomes to a certain extent, but increases substantially. A calculated simulation of this thesis is in reasonable agreement with the measurements... 

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. 

Oguchi, K., Ikegami, M., Jacobs, H., and Jobe, A. (1985). Clearance of large amounts of natural surfactants and liposomes of dipalmitoylphosphatidylcholine from the lungs of rabbits. Exp. Lung Res., 9, 221-235. 

Multilamellar liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and dicetyl phosphate (DCP) were prepared by the formation of a thin lipid film and subsequent sonication, and coated with chitosan (Ch) [36], Liposomes with a size of approximately 5 pm were used in the experiment. The Ch-coated and plain liposomes were compared in terms of mucoadhesion to the rat stomach and intestinal parts. Although both the liposomes were less adhesive to the stomach, Ch-coated liposomes displayed much higher mucoadhesion to all the intestinal parts in vitro than the plain liposomes. The intestinal adhesion of the plain liposomes were minimal. Further, Ch-coated liposomes showed a great mucoadhesion to the intestine at acidic and neutral pH values. This was also confirmed by fluorescence microscopy when pyrene-loaded Ch-coated liposomes were used in the mucoadhesion test. 

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. 

The quantum yield of photodissociation in neutral aqueous suspension of vesicles like egg lecithin (EL) and dipalmitoylphosphatidylcholine (DPPC) are significantly smaller than in the aqueous solution [83], INpOH (pKa = 9.2, pK a = 0.4) emits only from its DP form (2) in water. On incorporation into liposome membrane, a substantial increase of the P form (1) fluorescence is seen with concomitant decrease of DP form fluorescence. A similar effect is seen for 2NpOH with membrane incorporation. The biexponential fluorescence decay of the P form in fully incorporated naphthol suggests the presence of two localization sites... 

Another study on this same theme examined the effects of trehalose, glucose and hydroxyethyl starch on the motional properties of the phosphate headgroup of freeze-dried dipalmitoylphosphatidylcholine (DPPC) liposomes, this time employing 31P NMR.110 The work aimed to examine whether there... 

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). 

In PC and 1,2-dipalmitoylphosphatidylcholine (DPPC) liposomes below the phase transition temperature, pyrene senses an environment similar to butanol and propanol, respectively, although above the transition temperatures the environment is less polar [49c]. 

Differential Scanning Calorimetry (DSC) was applied in order to explore the interactions between each of four flavonoids Fig. (1) w ith dipalmitoylphosphatidylcholine (DPPC) membranes and to explain the variation of their incorporation efficiency into liposomes as well as the differences on the physicochemical properties of the liposomal formulations incorporating the isolated flavonoids [73-74]. 

Emulsions of water and CO2 have been used to form liposomes in one step without any organic solvent (57). The liposomes were made by forming a W/C emulsion stabilized with/L-i -dipalmitoylphosphatidylcholine. The pressure was reduced to form the liposomes by a reversed phase evaporation method. Large unilamellar liposomes with diameters of 0.1 to 1.2 pm were formed and used to trap D-( + )-glucose. 

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. 

Fig. 10 Release of entrapped 6-carboxyfluorescein from liposomes of monomeric (a) and polymeric (c) (11). For comparison DPPC (b) (dipalmitoylphosphatidylcholine).

The interesting property of the MPC copolymer is its affinity for phospholipids (5,72-74). The amount of a phospholipid, dipalmitoylphosphatidylcholine (DPPC), adsorbed on MPC copolymers was larger than that on polystyrene, poly(BMA) and poly(HEMA) and increased with increasing MPC moiety when the MPC copolymers were contacted with a liposomal solution of DPPC (5). This tendency was the same as that of the adsorption of phospholipid from human plasma which is indicated in Fig. 3. Thus, the affinity of poly(MPC-co-BMA) for the phospholipids could be observed even in the plasma. The DPPC molecules adsorbed on the poly(MPC-co-BMA) surface assumed an organized structure like that for a bilayer membrane, which was confirmed by differential scanning calorimetry(DSC) and X-ray photoelectron spectroscopy(XPS) when the poly(MPC-c -BMA) membrane was immersed in the solution containing DPPC (72,74) It is therefore concluded that the MPC copolymers stabilized the adsorption layer of phospholipids on the surface. Stabilization of the liposomal structure in water by a water-soluble MPC copolymer was also found (75). 

Recent research in our laboratory has opted to take an alternate approach in considering the interactions of alcohols with both the hydro-phobic interior and the previously overlooked lipid-water interface. Using H-NMR, it has been demonstrated that ethanol not only partitions to the interior of a membrane, it also binds in an apparently cooperative manner to the surface of model dipalmitoylphosphatidylcholine (DPPC) liposomes and synaptic plasma membranes. The surface binding of ethanol has an ordering effect at the lipid/water interface that opposes the previously observed disordering induced by the ethanol at the interior as determined by delayed Fourier transform spectroscopy (DFT H-NMR). Subsequently,... 

---