Doxorubicin uptake

Wong HL, Bendayan R, Rauth AM, Xue HY, Babakhanian K, WuXY. Amechanistic study of enhanced doxorubicin uptake and retention in multidrug resistant breast cancer cells using a polymer-lipid hybrid nanoparticle (PLN) system. J Pharmacol Exp Ther 2006 317 1372-1381. 

Serpe, M. J., K. A. Yarmey, et al. (2005). Doxorubicin uptake and release from microgel thin films. Biomacromolecules 6(1) 408-413. 

Figure 2 (A) Effect of incubation temperature on uptake of doxorubicin into 200 nm EPC/cholesterol (55 45 mol/mol) large unilamellar vesicles (LUVs) exhibiting a transmembrane pH gradient (pH 4 inside, 7.8 outside). Doxorubicin was added to LUVs (D/L = 0.3 wt wt) equilibrated at 21°C, 37°C, and 60°C. (B) Effect of cholesterol on the uptake of doxorubicin at 20 into lOOnm LUVs exhibiting a transmembrane pH gradient (pH 4.6 inside, 7.5 outside). Lipid compositions were EPC and EPC/cholesterol (1 1 mol/mol). The initial drug-to-lipid ratio was 100 nmol/pmol. Source Prom Refs. 12 (A), 21 (B).

The initial mixture and each time point are then assayed for doxorubicin and lipid. Lipid concentrations can be quantified by the phosphate assay (see above) or by liquid scintillation counting of an appropriate radiolabel. Doxorubicin is quantified by an absorbance assay (see below). The percent uptake at any time point (e.g., t = 30 minutes) is determined by %-uptake = [(D/L), =30minutes] x 100/[(D/L) inuiai]. Doxorubicin can be assayed by both a fluorescence assay and an absorbance assay, but we find the latter to be more accurate. The standard curve consists of four to five cuvettes containing 0 to 150 nmol doxorubicin in a volume of 0.1 mL samples to be assayed are of the same volume. To each tube is added 0.9 mL of 1% (v/v) Triton X-100 (in water) solution. For saturated lipid systems such as DSPC/Chol, the tubes should be heated in a boiling water bath for 10 to 15 seconds, until the detergent turns cloudy. Samples are allowed to cool, and absorbance is read at 480 nm on a UV/Visible spectrophotometer. 

The initial mixture and each time point are then assayed for ciprofloxacin and lipid. Lipid can be quantified using the phosphate assay (64,65) or by liquid scintillation counting. Ciprofloxacin is quantified by an absorbance assay following removal of drug from lipid by a Bligh-Dyer extraction procedure (78) (see below). The percent uptake is determined as described in the section Remote Loading of Doxorubicin into DSPC/Cholesterol (55 45) Large Unilamellar Vesicle. ... 

Mayer LD, Bally MB, Cullis PR, Wilson SL, Emerman JT. Comparison of free and liposome encapsulated doxorubicin tumor drug uptake and antitumor efficacy in the SCI 15 murine mammary tumor. Cancer Lett 1990 53 183. 

Miglietta A. et al., Cellular uptake and cytotoxicity of solid lipid nanospheres (SEN) incorporation doxorubicin or paclitaxel, Int. J. Pham., 210, 61, 2000. 

Doxorubicin is not absorbed orally, and because of its ability to cause tissue necrosis must not be injected intramuscularly or subcutaneously. Distribution studies indicate rapid uptake in all tissues except the CNS. Extensive tissue binding, primarily intranuclear, accounts for the prolonged elimination half-life. The drug is extensively metabolized in the liver to hydroxylated and conjugated metabolites and to aglycones that are primarily excreted in the bile. 

To increase the antiparasitic effect of methotrexate [254,255] and the more potent drugs doxorubicin [181] and muramyl dipeptide (MDP) [182], these drugs were coupled to manHSA. The beneficial effects of selective uptake of these drugs in KC was examined in mice infected with Leishmania parasites. These conjugates all inhibited the growth of these parasites in the macrophages predominantly in the liver but also in the spleen after repeated injections of the conjugate in leishmaniasis-infected mice. 

For example, surfaces comprising PNIPAM microgels were utilized for drug delivery [138], Electrostatic layer-by-layer assembly with poly(NIPAM-coacrylic acid) and poly(allylamine hydrochloride) on an amino-functionalized surface yielded thermoresponsive thin films. These were capable of a thermally regulated uptake and release of the chemotherapeutic drug doxorubicin. The films were loaded... 

The importance of uptake rates in relation to the RF was considered in a later paper [131] for four anthracyclines with identical amino sugar moiety (doxorubicin, daunorubicin, idarubicin, and 8(S)-fluoroidarubicin). The kinetics of uptake showed... 

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