PURPOSE Pharmacokinetic studies on liposomal drugs have previously measured total drug levels in tumors, which include non-bioavailable drug. However, drugs must be released from liposomes to have activity. We have developed a method for measuring levels of bioavailable (released) doxorubicin in vivo in tumors that will allow therapeutic activity to be correlated with bioavailable drug levels. ...

Cardiotoxicity from the antitumor anthracycline doxorubicin correlates with doxorubicin cardiac levels, redox activation to superoxide anion (O(2)(.-)) and hydrogen peroxide (H(2)O(2)), and formation of the long-lived secondary alcohol metabolite doxorubicinol. Cardiotoxicity may first manifest during salvage therapy with other drugs, such as the anthracenedione mitoxantrone. Minimal evidence f...

Doxorubicin is an excellent chemotherapeutic agent utilized for several types of cancer but the irreversible doxorubicin-induced cardiac damage is the major limitation for its use. Oxidative stress seems to be associated with some phase of the toxicity mechanism process. To determine if lycopene protects against doxorubicin-induced cardiotoxicity, male Wistar rats were randomly assigned either ...

Doxorubicin is an effective anthracycline used for cancer therapy. However, the clinical application of doxorubicin has been largely limited by its irreversible cardiotoxicity, which is mainly induced by the primary amine group. In this study, we structurally modified doxorubicin by converting the primary amine into an acid-labile amide before assessing the acute cardiac effect of doxorubicin (...

The purpose of the present study was to develop the Solutol HS15-based doxorubicin submicron emulsion with good stability and overcoming multi-drug resistance. In this study, we prepared doxorubicin submicron emulsion, and examined the stability after autoclaving, the in vitro cytotoxic activity, the intracellular accumulation and apoptpsis of doxorubicin submicron emulsion in MCF-7/ADR cells. ...

in this study, the interaction of the anthracycline antibiotic doxorubicin with dna-hmg 1 complex was investigated employing uv/vis spectroscopy, thermal denaturation and dna cellulose chromatography techniques. the results indicated that the binding of doxorubicin to the protein reduces its tm in a dose dependent manner. although doxorubicin protects free dna against thermal denaturation in th...

Acknowledgements I would like to extend my gratitude to my supervisor Sam Howison for his guidance and advice throughout the preparation and writing of this dissertation. I would also like to thank Christoph Reisinger for his advice whilst Dr Howison was away. Finally and most importantly I would like to thank my parents for their continued emotional and financial support, without which I would...

Sir, I was recently on call for nephrology, and something happened. I was rung by a first year junior doctor at 1 am, saying that a patient's 'MEWS score was 6'. The patient had had a renal transplant that day. A score of 6 is very high. It should trigger a rapid senior review, and possible intensive care re-ferral. Modified early warning score (MEWS) is an electronic early warning score based ...

Doxorubicin was intercalated into novel zirconium phosphate nano-platelets (ZrP). The obtained doxorubicin intercalated ZrP nano-platelets had an impressive 34.9% (w/w) drug loading. We used this material to deliver doxorubicin to breast cancer cells (MCF-7). Cellular studies with MCF-7 cells showed higher uptake and cytotoxicity of doxorubicin loaded ZrP compared to free doxorubicin.

The quinonoid anthracycline, doxorubicin (Adriamycin) is a potent anti-neoplastic agent whose clinical use is limited by severe cardiotoxicity. Mitochondrial damage is a major component of this cardiotoxicity, and rival oxidative and non-oxidative mechanisms for inactivation of the electron transport chain have been proposed. Using bovine heart submitochondrial preparations (SMP) we have now fo...