Monday, 23 May 2005 - 10:30 AM

This presentation is part of: Nanoparticles, Microparticles and Vesicles

In Vivo and In Vitro Elution of NSAID and Drugs from Self-Delivering PolyNSAIDs Microspheres

Yun H. Choe, Zheng Wang, Bryant J. Pudil, Michael B. Hicks, Suseela Kanamathareddy, Stephen Goodrich, and Alan Letton. Polymerix Corporation, Piscataway, NJ

The use of biodegradable polymers for drug delivery from microspheres demands a system that eliminates inflammation, pain and other side effects associated with current technology. Our approach utilizes anhydride bonds in the polymer where NSAIDs were polymerized to be part of the backbone, as first reported by K.E. Uhrich. In a continuation of this effort, we prepared microspheres from a series of PolyNSAIDs containing two well known NSAIDs, salicylic acid and diflunisal (DF), and studied their elution in vitro using several media including serum. In a rat subcutaneous PK model, we demonstrated the controlled and prolonged release of NSAIDs relative to standard oral NSAID dosing. PolyNSAIDs were prepared either by a melt-polycondensation or a proprietary solution method and the microspheres by oil in water emulsion method. When rats were administered a single subcutaneous injection of 250 mg PolyDF microspheres, containing about 192 mg DF formulated in a standard aqueous vehicle, peak plasma level of DF (35 μg/mL) were achieved within two days. Thereafter the drug level declined slowly over about two weeks. In contrast, a single oral dose (25 mg) of DF produced a drug level that declined within a few hours. We also have prepared a series of PolyNSAID microspheres where we ad-mixed several drugs, e.g. methotrexate. We have confirmed that the rate of breakdown of microspheres can be affected by the surface area of the spheres, by types of bonds between the NSAID and linker, and by types of anhydride bonds incorporated among the aromatic structures.

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