Drug delivery of anticancer agents: water soluble 4-poly (ethylene glycol) derivatives of the lignan, podophyllotoxin
| Autor: | Yun H. Choe, Richard B. Greenwald, Charles D. Conover, Anthony Martinez, Shuiyun Guan, Annapurna Pendri, Dechun Wu, Kwok L. Shum, Zuliang Yao |
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| Rok vydání: | 1999 |
| Předmět: |
Lung Neoplasms
Transplantation Heterologous Mice Nude Pharmaceutical Science Polyethylene glycol Pharmacology Polyethylene Glycols Inhibitory Concentration 50 Mice chemistry.chemical_compound In vivo PEG ratio Tumor Cells Cultured medicine Animals Humans Nuclear Magnetic Resonance Biomolecular Podophyllotoxin Drug Carriers Leukemia P388 Water Biological activity Antineoplastic Agents Phytogenic Transplantation Solubility chemistry Biochemistry Drug delivery Female Drug Screening Assays Antitumor Drug carrier Neoplasm Transplantation medicine.drug |
| Zdroj: | Journal of Controlled Release. 61:281-294 |
| ISSN: | 0168-3659 |
| Popis: | This paper reports on the synthesis and in vivo oncolytic activity of a series of water-soluble acyl derivatives of polyethylene glycol (PEG) conjugated podophyllotoxin. Some analogs of the polymer conjugate showed significantly better activity in a murine leukemia model than native podophyllotoxin suspended in an intralipid emulsion. Additionally, when tested intravenously against a solid lung tumor (A549) model, some conjugated analogs were equivalent to the podophyllotoxin/intralipid emulsion, while those compounds demonstrating slower rates of plasma hydrolysis (in vitro) appeared to cause greater toxicity. There appeared to be an overall correlation between the in vivo antitumor activity of the conjugate and its rate of hydrolysis in vitro, with those showing faster release possessing greater antitumor activity. In conclusion, the solubilization and predictable release of podophyllotoxin from a PEG carrier was achieved and resulted in some derivatives demonstrating, at a minimum, equivalency with podophyllotoxin when administered on an equal molar basis. Further studies may be warranted to assess the PEG-conjugates pharmacokinetics and therapeutic indices in leukemic models. |
| Databáze: | OpenAIRE |
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