Liposome tissue distribution

This section will briefly discuss the clearance kinetics and tissue distribution of liposomes in vivo (reviewed by Senior, 1987 Hwang, 1987 Gregoriadis, 1988a Hwang end Beaumier, 1988 Juliano, 1988). Liposomes, when administered in vivo by a variety of routes, rapidly accumulate in the mononuclear phagocyte system (MPS), also referred... 

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). 

Chronic liposome administration in mice Effects on reticuloendothelial function and tissue distribution, J. Pharmacol. Exp. Ther.. 229, 267-275. 

Ellens, H., Morselt, H. W. M., Dontje, B. H. J., Kalicharan, D., Hulstaert, C. E., and Scherphof, G. L. (1983). Effects of liposome dose and the presence of lymphosarcoma cells on blood clearance and tissue distribution of large unilamellar liposomes in mice, Cancer Res.. 43. 2927-2934. 

Gregoriadis, G. (1988a). Fate of injected liposomes Observations on entrapped solute retention, vesicle clearance and tissue distribution in vivo, in Liposomes as Drug Carriers Recent Trends and Progress (G. Gregoriadis, ed.), John Wiley and Sons, Chichester, pp. 3-18. 

Juliano, R. L. (1988). Factors effecting the clearance kinetics and tissue distribution of liposomes, microspheres and emulsions,... 

Lautersztain, J., Perez-Soler, R., Khokhar, A. R., Newman, R. A., and Lopez-Berestein, G. (1986). Pharmacokinetics and tissue distribution of liposome-encapsulated cis-bis-N-decyUminodiacetato-... 

Altered tissue distribution of amphotericin B by liposomal encapsulation Comparison of normal mice and mice infected with Candida albicans. Cancer Drug Deliv., 1, 199-205. 

When liposomes are formed, they can be made to entrap certain compounds inside themselves, eg, drugs and isolated genes. There is interest in using liposomes to distribute drugs to certain tissues, and if components (eg, antibodies to certain cell surface molecules) could be incorporated into liposomes so that they would be targeted to specific tissues or tumors, the therapeutic impact would be considerable. DNA entrapped inside liposomes appears to be less sensitive to... 

Tissue distribution of lipo-preparations. The tissue distribution of lipid microspheres in normal and pathologic animals was studied. Research into liposomes of similar size suggested that lipid microspheres accumulated preferentially in the reticuloendothelial system, inflammatory sites, or certain tumors. The distribution of lipid microspheres to these tissues has been found in our studies (7,2). Interestingly, our study showed that lipid microspheres accumulated, particularly at high concentrations, in damaged vascular walls such as atherosclerotic vascular walls. 

Because the size and surface net charge of liposomes can also influence the rate and extent of tissue distribution, these characteristics could be used for target-specific delivery of liposome-encapsulated proteins and drugs. These issues will be discussed later in the context of Site-specific delivery strategies. ... 

A number of factors for DOTAP-cholesterol/DNA complex preparation including the DNA/liposome ratio, mild sonication, heating, and extrusion were found to be crucial for improved systemic delivery maximal gene expression was obtained when a homogeneous population of DNA/liposome complexes (200-450 nm) was used. Cryoelectron microscopy showed that the DNA was condensed on the interior of liposomes between two lipid bilayers in these formulations, a factor that was thought to be responsible for the high transfection efficiency in vivo and for the broad tissue distribution (150). 

K. M. Wasan, K. Vadiei, G. Lopez-Berenstein, and D. R. Luke, Pharmacokinetics, tissue distribution and toxicity of free and liposomal amphotericin B in diabetic rats, J. Infect. Dis. 161 562-566 (1990). 

Gabizon, A., Shiota, R., and Papahadjopoulos. D. (1989), Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times, J. Nat. Can. Inst., 81,1484-1488. 

Sadzuka, Y., and Hirota, S. (1998), Does the amount of an antitumor agent entrapped in liposomes influence its tissue distribution and cell uptake Cancer Lett., 131, 163-170. 

Senior, J., Crawley, J. C. W., and Gregoriadis, G. (1985),Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection, Biochim. Biophys. Acta, 839,1-8. 

Biodistribution of liposomes is a very important parameter from the clinical point of view. Liposomes can alter both the tissue distribution and the rate of clearance of the drug by making the drug take on the pharmacokinetic characteristics of the carrier (10, 11). The pharmacokinetic variables of the liposomes depend on the physiochemical characteristics of the liposomes, such as size, surface charge, membrane lipid packing, steric stabilization, dose, and route of administration. As with other microparticulate delivery systems, conventional liposomes are vulnerable to elimination from systemic circulation by the cells of the reticuloendothelial system (RES) (12). The primary sites of accumulation of conventional liposomes are the tumor, liver, and spleen compared with non-liposomal formulations (13). Many studies have shown that within the first 15-30 min after intravenous administration of liposomes between 50 and 80% of the dose is adsorbed by the cells of the RES, primarily by the Kupffer cells of the liver (14-16). 

The tissue distribution of liposomes throughout the whole body in experimental systems can be clearly determined by measuring the concentration of markers (preferably radioactive) in the blood or in each individual organ. 

Saito K, Ando J, Yoshida M, et al. Tissue distribution of sialoglycopeptide bearing liposomes in rats. Chem Phann Bull 1988 36 4187-4191. 

Kim CK, Lee MK, Han JH, et al. Pharmacokinetics and tissue distribution of methotrexate after intravenous injection of differently charged liposome-entrapped methotrexate to rats. Int J Pharm 1994 108 21-29. 

The concept behind the use of liposomes as carriers of drugs and macromolecules is related to an expected protection of the encapsulated molecules in the blood stream, an altered tissue distribution and pharmacokinetics, as well as an increased uptake into cells by mechanisms that are not normally available for these molecules. Some of these expectations have been verified through studies in various laboratories during the last few years. Such studies have shown that liposome encapsulation can alter drastically the pharmacokinetics and tissue disposition of the encapsulated substances, it can enhance their uptake into cells, and it can Increase their pharmacological efficacy. Several recent reviews have discussed these early results in considerable detail. 20... 

Tissue Disposition and Pharmacological Effects of Liposomes In Vivo -Since the initial publication of studies involving injection of liposome-entrapped substances In vivo,H 71.72 there has been an increasing number of studies on both the altered tissue distribution and also on the increased pharmacological efficacy of encapsulated agents. The subject has been reviewed recently.13 15,20, The most important points for future consideration include the permeability properties of liposomes in a physiological environment, their interaction with plasma components, the role of liposome size and chemistry in determining the rate of removal from the circulation and their tissue localization at the cellular level. 

In large-cell lymphoma, a liposomal formulation of vincristine (ONCO-TCS), given in doses of 2 mg/m , has less neurotoxicity and retains activity in patients who relapse after vincristine therapy. It has the expected advantages of slower elimination and greater tissue distribution as compared to the unmodified drug. 

Fielding R M, Lewis R O, Moon-McDermott L (1998). Altered tissue distribution and elimination of amikacin encapsulated in unilamellar, low-clearance liposomes (MiKasome). P/zarw. Res. 15 1775-1781. 

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