Minor pathological changes are induced by naltrexone-poly (DL-lactide) implants in pregnant rats

W.O. Farid, D. Mccallum, Robert Tait, Sarah Dunlop, Gary Hulse

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    Abstract

    Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13–26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
    Original languageEnglish
    Pages (from-to)964-974
    JournalJournal of Biomedical Materials Research Part A
    Volume91A
    Issue number4
    DOIs
    Publication statusPublished - 2009

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