Drug-liposome interaction

Avdeef A, Box KJ, Comer EA et al. (1998) pH metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm Res 15 209-215 Baird CL, Courtenay ES, Myszka DG (2002) Surface plasmon resonance characterization of drug/liposome interactions. Anal Biochem 310 93-99... 

In terms of structural chemistry, liposomes are supramolecular aggregates. A drug will also associate with the liposome by via non-covalent binding. With modified and unmodified ODNs, liposomes have become a particularly promising approach, aided by the fact that specific ODN-modifications may also be used specifically to influence drug-liposome interaction. Thus, base-modified cholesterol derivatives have been developed to act as specific anchor points for ODNs in liposomal formulations [397-408], Application of pH-sensitive liposomes made from DOPE/OA [409] or DOPE/OA/CHOL [410] has also been suggested. As a first important effect of liposome formulation, protection of ODNs from extracellular nucleases has been observed [411-413]. Use of such formulations has proven to be a valid method for cellular internalization in cultured cell lines, an effect which has been reviewed by a number of authors [414,415]. 

Lundahl, P., Beigi, F. Immobilized liposome chromatography of drugs for model analysis of drug-membrane interactions. Adv. Drug Deliv. Rev. 1997, 23, 221-227. 

Artificial membranes are used to study the influence of drug structure and of membrane composition on drug-membrane interactions. Artificial membranes that simulate mammalian membranes can easily be prepared because of the readiness of phospholipids to form lipid bilayers spontaneously. They have a strong tendency to self-associate in water. The macroscopic structure of dispersions of phospholipids depends on the type of lipids and on the water content. The structure and properties of self-assembled phospholipids in excess water have been described [74], and the mechanism of vesicle (synonym for liposome) formation has been reviewed [75]. While the individual components of membranes, proteins and lipids, are made up of atoms and covalent bonds, their association with each other to produce membrane structures is governed largely by hydrophobic effects. The hydrophobic effect is derived from the structure of water and the interaction of other components with the water structure. Because of their enormous hydrogen-bonding capacity, water molecules adopt a structure in both the liquid and solid state. 

Liposome preparations have been shown to be suitable not only for studying special drug-membrane interaction effects in vitro but also for use as drug carriers. Various techniques have been developed and described to prepare homogeneous unil-... 

Liposomal preparations are of interest for studying not only drug-membrane interactions but also membrane permeability and drug transport... 

Several other examples of drug-membrane interactions have been reported. Using X-ray diffraction techniques, interactions with tetracyclines [75], pindolol [76], and chlorpromazine [77, 78] have been described. In these studies, it was shown that in the presence of chlorpromazine the bilayer thickness or lipid head group separation in DPPC liposomes is only 30 A, which is about 20 A smaller than two fully extended DPPC molecules. Chlorpromazine produced an interdigitated phase, which is in agreement with the observed effect of chlorpromazine on the shape of erythrocytes. 

The results again show that liposome partitioning gives superior information and describes biological effects related to drug-membrane interactions more correctly than log Poet especially in the case of charged drug molecules. 

Mohr, K. and Struve, M., Differential influence of aruonic and cationic charge on the ability of amphiphilic drugs to interact with DPPC-liposomes, Biochem. Pharmacol., 41, 961,1991. 

Lundahl P and Beigi F. Immobilized Liposome Chromatography of Drugs for Model Analysis of Drug-Membrane Interactions. Adv Drug Deliv Rev 1997 23 221-227. 

Brack A, Abu-Dahab R, Borchard G, et al. Lectin-functionalized liposomes for pulmonary drug delivery interaction with human alveolar epithelial cells. J Drug Target 2001 9 241. 

Immobilized artificial membrane (lAM) stationary phase consists of a monolayer of phospholipid covalently immobilized on an inert silica support. The lAM stationary phase mimics the lipid environment found in cell membranes, and it can be used for elucidating drug-membrane interactions. The interaction of catechins, flavones, flavonols, anthocyanidins, and anthocyanins with phosphatidylcholine was investigated by HPLC with an lAM colunm. The lAM partition coefficients of the flavonoids correlated well with the amounts flavonoids incorporation into the liposomes [42]. 

Glycosteroids in vesicles and liposomes, interactions with membranes, drug transport and solubilization... 

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