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Investigations of the biodistribution and phototherapeutic utility of two palladium(II)-containing macrocyclic drugs in a tumour-bearing mouse model: A study of the pharmacokinetics and tissue distribution of the potential photodynamic drug palladium-bac

Posted on:2003-03-02Degree:M.ScType:Thesis
University:Royal Military College of Canada (Canada)Candidate:DeGroot, Jennifer LeanneFull Text:PDF
GTID:2464390011988239Subject:Chemistry
Abstract/Summary:
The use of palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8 ) in the photothermal treatment of EMT6 tumours subcutaneously implanted in Balb/c mice using an 828 nm CW diode laser was investigated. Treatment parameters were chosen based on the results of a previous pharmacokinetic study and theoretical calculations of predicted temperature rise in the tumour and surrounding tissue. Gross and histological examination of the treated tumours indicated few cases of selective tumour destruction, with extensive skin damage being noted in most cases where any significant tumour damage was found to occur. Photothermal therapy using this drug therefore appeared to be ineffective under the conditions of this study. Many uncontrolled variables influenced the outcomes of this study however, and therefore, this evaluation of the effectiveness of the drug may be biased.; One of the variables potentially affecting the outcome of the treatment study was the fact that the tumour location was changed, for the irradiation experiments, from that of the previous pharmacokinetic study. As a result, the tissue distribution of PdNc(OBu)8 in the serum, muscle, skin and tumour at 72, 96, and 120 hours post intraperitoneal injection was re-determined in order to verify the concentration of the drug in the tumour, located in the new location, around the treatment time point. The results of this study indicated low accumulation of PdNc(OBu)8 in the tumour and muscle with relatively high levels being present in the skin. These results are not conducive to effective treatment with this drug and therefore provide some explanation for the adverse results obtained in the treatment study. In addition, based on the tumour concentration found, it is likely that the irradiation laser did not provide high enough fluence for treatment to have been effective.
Keywords/Search Tags:Tumour, Drug, Tissue
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