Liposomes charged

Liposome (charge) pH Inhibition period, min Inhibition rate constant,... 

The most evident approaches to modify the sinface properties of liposomes are (1) to vary liposome compositions (resulting in a variation of liposome charges and phase states) and (2) to attach some nonphospholipid compounds to the liposome surface. Various modifiers have been suggested for controlling the distribution and in vivo properties of liposomes [27-30]. The most important and well-studied modifiers are as follows ... 

Figure 4 Effect of modified and unmodified poly(MA-DP)s on the stability of the negatively charged liposome. = unmodified MA-DP = MA-DP-A20 = MA-DP-H68.

Figure 6 Effect of low-molecular weight (3,400) po-ly(MA-CDA)s on the stability of negatively charged liposome. = unmodified MA-CDA-3.4K = MA-CDA-3.4K-A18 = MA-CDA-3.4K-H27.

Liposomes are members of a family of vesicular structures which can vary widely in their physicochemical properties. Basically, a liposome is built of one or more lipid bilayers surrounding an aqueous core. The backbone of the bilayer consists of phospholipids the major phospholipid is usually phosphatidylcholine (PC), a neutral lipid. Size, number of bilayers, bilayer charge, and bilayer rigidity are critical parameters controlling the fate of liposomes in vitro and in vivo. Dependent on the preparation procedure unilamellar or multilamellar vesicles can be produced. The diameter of these vesicles can range from 25 nm up to 50 ym—a 2000-fold size difference. 

The surface potential can play an important role in the behavior of liposomes in vivo and in vitro (e.g.. Senior, 1987). In general, charged liposomes ai e more stable against aggregation and fusion than uncharged vesicles. However, physically stable neutral liposomes have been described (e.g.. Van Dalen et al., 1988). They are sufficiently stabilized by repulsive hydration forces, which counteract the attractive van der Waals forces. 

The presence of impurities like free fatty acids in egg or soybean phosphatidylcholine, or in the (semi)synthetic phosphatidylcholines (e.g., DMPC, DPPC, DSPC) can be detected by monitoring the electrophoretic behavior of liposome dispersions of these phospholipids in aqueous media with low ionic strength a negative charge will be found on these liposomes when free fatty acids are present in the bilayers. 

The behavior of liposomes in vivo can be influenced to a considerable extent by varying chemical composition and physical properties. Parameters affecting rate of clearance from the blood and tissue distribution include size, composition, dose, and surface characteristics (e.g., charge, hydrophobicity, presence of homing devices such as antibodies). 

In addition to size and charge, the chemical composition of liposomes affects their in vivo fate. For example, it has been shown... 

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

The effects of liposome size and surface charge on liposome-mediated delivery of methotrexate-gamma-aspartate to cells in vitro, Biochim. Biophys. Acta, 820, 74-84. 

Juliano, R. L., and Stamp, D. (1975). Effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs, Biochlm. Biophys. Res. Commun.. 63, 651-658. 

Straubinger, R. M., Lopez, N. G., Debs, R. J., Hong, K., and Papahadjopoulos, D. (1988). Liposome-based therapy of human ovarian cancer Parameters determining potency of negatively charged and antibody-targeted liposomes, Cancer Res.. 48, 5237-5245. 

Coating positively charged liposomes resulted in inversion of the J-potential [119]... 

In order to enhance the stability of hposomes and to provide a biocompatible outermost surface shucture for controlled immobihzation (see Section IV), isolated monomeric and oligomeric S-layer protein from B. coagulans E38/vl [118,123,143], B. sphaericus CCM 2177, and the SbsB from B. stearothermophilus PV72/p2 [119] have been crystallized into the respective lattice type on positively charged liposomes composed of DPPC, HD A, and cholesterol. Such S-layer-coated hposomes are spherical biomimetic structures (Fig. 18) that resemble archaeal ceUs (Fig. 14) or virus envelopes. The crystallization of S-... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

For multi-pH liposome-water distribution measurements in 0.15 M NaCl or KCl solutions, the difference between the true pKj and pK (and between logPMBM and logPMBM) is about 1 log unit for bases and 2 log units for acids. Liposomes formed from phosphatidylcholine have a tendency to stabilize the charged drug more effectively than that in the octanol-water system [71]. Table 3.1 shows liposome-water examples of the relative pKj shifts. The average values cited in the examples are close the diff 1-2 approximation noted above. 

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