Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
MetadataShow full item record
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 longterm 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.
Showing items related by title, author, creator and subject.
Biodegradability of naltrexone-poly(DL) lactide implants in vivo assessed under ultrasound in humansHulse, G.; Low, V.; Stalenberg, V.; Morris, N.; Thompson, R.; Tait, Robert; Phan, C.; Ngo, H.; Arnold-Reed, D. (2008)Ultrasound was used to assess the in vivo biodegradability of a sustained release poly(DL)lactide naltrexone implant in 71 persons previously treated for heroin dependence. We assessed 139 implant sites ranging from 2 to ...
Li, J.; Zheng, W.; Zheng, Y.; Lou, Xia (2011)The objective of this study was to investigate the hemocompatibility and cell responses to some novel poly(L-lactide) (PLA) composites containing surface modified hydroxyapatite particles for potential applications as a ...
Ngo, H.; Arnold-Reed, D.; Hansson, R.; Tait, Robert; Hulse, G. (2008)Aims: Oral naltrexone is used in the management of both heroin and alcohol dependence. However, poor compliance has limited its clinical utility. The study's objective was to determine the period of therapeutic coverage ...