Biodistribution liposomes

Bilayer rigidity is a parameter which influences biodistribution and biodegradation of liposomes. In vitro a hydrophilic marker molecule (carboxyfluorescein) leaked much faster from the vesicles with bilayers in a fluid state than from bilayers in a gel state (Crommelin and Van Bommel, 1984). An indication of the bilayer rigidity can... 

Parker, R. J., Priester, E. R., and Sieber, S. M. (1982). Comparison of lymphatic uptake metabolism, excretion, and biodistribution of free and liposome-entrapped (l cjcytosine beta-D-arabinofuranoside following intraperitoneal administration in rats, Drug. Me tab. Dispos., 10, 40-46. 

Liposomes represent an important class of carrier vehicles other than polymers for drug delivery. This paper provides an introduction and general review of liposomes with emphasis on their classifications, their constituent materials, their preparation and characterizaton, and their stability and biodistribution in the body. Liposomes with specific characteristics are also described in this general introduction. 

Chang CW, Barber L, Ouyang C, Masin D, Bally MB, Madden TD. Plasma clearance, biodistribution and therapeutic properties of mitoxantrone encapsulated in conventional and sterically stabilized liposomes after intravenous administration in BDFl mice. Br J Cancer 1997 75 169. 

In earlier studies, the duplex drugs 5-FdU-NOAC and ara-C-NOAC were found to be strong inhibitors of the cell cycle, mainly arresting tumor cells in the early S-phase (33,46 8). However, with liposome formulations of the duplex drugs cell uptake, intracellular distribution, biodistribution, and metabolism were not yet investigated in details. Due to their similarity to NOAC, it can be assumed that they have comparable pharmacological... 

Rudolph AS, Klipper RW, Goins B, et al. In vivo biodistribution of a radiolabeled blood substitute Tc-labeled liposome-encapsulated hemoglobin in an anesthetized rabbit. Proc Natl Acad Sci USA 1991 88 10976. 

Awasthi VD, Garcia D, Goins BA, et al. Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits. Int J Pharm 2003 253 121. 

Liu D, Mori A, Huang L. Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GMl-containing liposomes. Biochim Biophys Acta 1992 1104 95. 

Rudolph AS, Cliff RO, Klipper R, et al. Circulation persistence and biodistribution of lyophilized liposome-encapsulated hemoglobin an oxygen-carrying resuscitative fluid. Crit Care Med 1994 22 142. 

Charrois GJ, Allen TM. Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer. Biochim Biophys Acta 2004 1663(1-2) 167. 

The HMPAO-glutathione method has been used in a number of preclinical animal studies (19). An example is shown in Figure 1, where the biodistribution of Tc-HMPAO-labeled PEG liposomes is compared to... 

The same liposomal preparation was used to investigate the effect of the administered dose on the biodistribution and pharmacokinetics (41). The effect of the lipid dose of Tc-HYNIC-PEG-liposomes was investigated in the low-dose range (0.02-1.0 pmol/kg), typically for noninvasive imaging applications. The biodistribution and pharmacokinetics of "Tc-HYNIC-PEG-liposomes at various dose levels were studied in rats and rabbits with a focal Escherichia coli infection. Moreover, the pharmacokinetics of Tc-HYNIC-PEG-liposomes at two lipid dose levels were studied in four patients. In rabbits, enhanced clearance was observed at a dose level of 0.02 pmol/kg. The circulatory half-life decreased from 10.4 to 3.5 hours (at 1.0 and 0.02 pmol/kg, respectively). At the lowest dose level, liposomes were mainly taken up by the liver and to a lesser extent by the spleen. Most importantly, the rapid clearance of low-dose PEG liposomes was also observed in humans when relatively low lipid doses were administered as is shown in Figure 4. This study showed that, at very low lipid doses, the biodistribution of PEG liposomes is dramatically altered. 

Goins B, Phillips WT. Radiolabelled liposomes for imaging and biodistribution studies. In Torchilin VP, Weissig V, eds. Liposomes A Practical Approach. Oxford, U.K. Oxford University Press, 2003 319. 

Awasthi VD, Goins B, Klipper R, Phillips WT. Dual radiolabeled liposomes biodistribution studies and localization of focal sites of infection in rats. Nucl Med Biol 1998 25 155. 

Bao A, Goins B, Klipper R, Negrete G, Phillips WT. Re-Liposome labeling using Re-SNS/S complexes in vitro stability imaging biodistribution in rats. 

Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug s functional properties relative to those of the unencapsulated or nonlipid-associated drug. Lipid-based formulations increase the circulation time and alter the biodistribution of associated amphotericin. Increasing drug levels at site of action and reducing levels in normal tissues offers 2 distinct clinical advantages An increased therapeutic index and altered toxicity profile relative to free drug. 

It is well established that size, charge, and chemical composition of liposomes affect their fate in vivo [306], To manipulate their biodistribution and/or drug release, liposomes of different structures have been prepared, including those sensitive to changes in pH [307, 308] or temperature [309,310]. Compared to soluble polymers discussed in previous chapters, liposomes, when applied i.v., are captured by a substantially greater extent by the specialized cells (macrophages) of the reticuloendothelial system (RES) [311]. The removal of liposomes from the bloodstream takes place by nonspecific endocytosis (phagocytosis) [312],... 

Ishiwata, H., Suzuki, N., Ando, S., Kikuchi, H., Kitagawa, T. (2000). Characteristics and biodistribution of cationic liposomes and their DNA complexes. J. Control... 

The charge on the liposomal surface is a property that has major effects on the stability, biodistribution, and cellular uptake of liposomes, and is governed by lipid headgroup composition and by pH. It can be monitored by micro electrophoresis (i.e., capillary zone electrophoresis), or by measurement of the zeta potential (Egorova, 1994). 

We examined the biodistribution of cationic liposomes/pDNA complex following intravenous injection in mice and pharmacokinetically analyzed the data based on the clearance concept (Mahato etal., 1995a, 1997). These analyses showed that the pharmacokinetics of 32P-pDNA complexes depend on their mixing (charge) ratio, the type of cationic and helper lipids (Mahato et al., 1998). When analyzed using radioactivity counting following the injection of the complex prepared with 32P-pDNA, the tissue uptake clearance per g... 

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