Title page for ETD etd-05122008-133405

Document Type Doctoral Thesis
Author Visser, Suzaan
URN etd-05122008-133405
Document Title The toxicity and therapeutic index of a methotrexate polymeric compound, D-85
Degree MSc (Pharmacology)
Department Pharmacology
Advisor Name Title
Prof J R Snyman Co-Supervisor
Prof C E Medlen Supervisor
  • cytotoxic
  • methotrexate
  • cancer
Date 2007-11-23
Availability unrestricted
Methotrexate (MTX) has been used for many years in the treatment of patients with cancer as a cytotoxic agent and as an anti-inflammatory drug for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA). However, because of the side effects associated with MTX, there is a continuous search for drugs with less toxicity and hence a greater therapeutic index. In pursuit of a better and less toxic compound, researchers have coupled MTX to various polymeric drug carriers.

The objective of this study was to evaluate methotrexate and a methotrexate polymer (D-85) in in vitro and in vivo systems. It was hypothesized that D-85 would show improved anti-neoplastic and anti-inflammatory properties with decreased toxicity compared to MTX. The in vitro experiments included cell viability assays on cancerous and non-cancerous cell lines in order to compare the effects of the two drugs on normal and cancerous cells. Other in vitro assays were performed to assess the effect of the two compounds on cell cycle and mixed lymphocyte cultures. Finally, the toxic effects of both drugs were studied concentrating on two treatment regimens, namely that of an anti-inflammatory regimen and a chemotherapeutic regimen.

The results obtained during this study clearly illustrate the chemotherapeutic and anti-rheumatic activity of the two drugs, MTX and D-85. The methotrexate water-soluble drug D-85, however showed greater toxicity towards normal cells compared to the toxicity of methotrexate.

University of Pretoria 2007


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