In vitro release of hydrophobic drugs from polyanhydride disks.
We have evaluated the feasibility of using polyanhydride disks containing hydrophobic antiproliferative agents for controlled drug release after glaucoma filtration surgery. Taxol and VP-16 were the most potent inhibitors of fibroblast proliferation tested, with ID50s of 3 ng/mL and 200 ng/mL, respectively. In vitro release of taxol occurred at concentrations exceeding its ID50 for at least 100 days; VP-16 was released for 31 days. The media into which the drugs were released were able to inhibit fibroblast proliferation in vitro, indicating that the bioactivity of the drugs withstood incorporation into, and release from, the polyanhydride. Polyanhydride disks containing taxol and VP-16 merit testing in animal models of glaucoma filtration surgery.
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.
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Jampel
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Koya
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Leong
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Quigley
D000470:Alkaloids / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D004343:Drug Implants; D005047:Etoposide / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects*; D005467:Floxuridine / Q000493:pharmacokinetics / Q000633:toxicity; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000633:toxicity; D005901:Glaucoma / Q000601:surgery*; D006801:Humans; D015122:Mercaptopurine / Q000493:pharmacokinetics / Q000633:toxicity; D017239:Paclitaxel; D011108:Polymers; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control*; D014750:Vincristine / Q000493:pharmacokinetics / Q000633:toxicity
D000470:Alkaloids; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D004343:Drug Implants; D011108:Polymers; D005467:Floxuridine; C045869:polybis(carbophenoxypropane); D014750:Vincristine; D005047:Etoposide; C011107:sebacic acid; D015122:Mercaptopurine; D017239:Paclitaxel; D005472:Fluorouracil