Poly (Dl-Lactic-Co-Glycolic Acid) microparticles and synthetic peptide drug conjugate for anti-cancer drug delivery

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2009

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Şen, Gülseren Petek

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Cancer is a group of diseases in which normal cells are converted to cells capable of autonomous growth and invasion. In the chemotherapeutic control of cancer, drugs are usually given systemically so they reach toxic levels in healthy cells as well as cancer cells. This causes serious side effects. Another important problem with chemotherapy is resistance developed to cytotoxic drugs (multi drug resistance). Doxorubicin (Dox) occupies a central position in the treatment of breast cancer. However doxorubicin induced cardiac toxicity is associated with a high incidence of morbidity and mortality. Resistance of malignant tumors to Dox is another important cause of treatment failure in patients with cancer. One approach to overcome Dox-related toxicity is to use polymeric drug carriers, which direct the Dox away from heart tissue, and allow usage of lower dosages. In this present study two different anti-cancer drug delivery methods were evaluated. Dox was encapsulated in PLGA microparticles by single and double microemulsion solvent evaporation techniques. The highest entrapment of doxorubicin within PLGA microspheres obtained by optimization of process parameters. A sustained release of doxorubicin was obtained for 20 days. Several protein transduction domains are known to have the ability to pass through biological membranes. One such peptide is HIV-1 TAT. In this study TAT was evaluated for its ability to carry Dox into Dox resistant MCF-7 tumor cells. Dox peptide conjugate was more potent than free drug. The concentration of drug in resistant cancer cells was increased indicating a partial reversal of drug resistance.

Subject Keywords

Biotechnology., Transduction Domain.

URI

http://etd.lib.metu.edu.tr/upload/12611405/index.pdf
https://hdl.handle.net/11511/19245

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

G. P. Şen, “Poly (Dl-Lactic-Co-Glycolic Acid) microparticles and synthetic peptide drug conjugate for anti-cancer drug delivery,” M.S. - Master of Science, Middle East Technical University, 2009.