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

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 possessed; 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. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91A: 964-974, 2009