Development of a poly(ortho ester) prototype with a latent acid in the polymer backbone for 5-fluorouracil delivery.
A study has been carried out to determine whether the latest family of poly(ortho esters) can be converted into a practical delivery system. This polymer differs from the previously described polymers in that it incorporates a short segment of a latent acid in the polymer backbone. The following issues were specifically addressed: (a) can the erosion and drug release be reproducibly controlled to yield the desired drug release kinetics and erosion rates? (b) Is the polymer stable during radiation sterilization, on storage and on fabrication? (c) Can the polymer be prepared reproducibly at the desired molecular weights and molecular weight distribution? (d) Is the polymer safe for its intended application and does the in vivo erosion proceed to completion? (e) Can the polymer be easily fabricated into desired configurations? Studies have shown that if the synthesis is carefully controlled, the desired molecular weights can be reproducibly prepared, that the polymer is reasonably stable after irradiation at 24 kGy and during storage at room temperature under anhydrous conditions, and that it can be safely thermally fabricated at temperatures in the neighborhood of 120 degrees C. When polymer devices were implanted intraperitoneally in rats the polymer eroded to completion without any overt toxicity as determined by the measured parameters.
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Advanced Polymer Systems, 123 Saginaw Drive, Redwood City, CA 94063, USA.
Shen
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Lopez
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Zherebin
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Barr
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Schacht
E
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Heller
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D000143:Acids; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001610:Beta Particles; D002384:Catalysis; D004339:Drug Compounding; D004343:Drug Implants; D004355:Drug Stability; D004356:Drug Storage; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007700:Kinetics; D008422:Materials Testing; D008970:Molecular Weight; D014677:Pharmaceutical Vehicles / Q000737:chemistry* / Q000528:radiation effects; D011091:Polyesters / Q000737:chemistry* / Q000528:radiation effects; D051381:Rats; D012995:Solubility; D013242:Sterilization
D000143:Acids; D000964:Antimetabolites, Antineoplastic; D004343:Drug Implants; D014677:Pharmaceutical Vehicles; D011091:Polyesters; D005472:Fluorouracil