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 th...

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Main Authors: Farid, W., McCallum, D., Tait, Robert, Dunlop, S., Hulse, G.
Format: Journal Article
Published: 2009
Online Access:http://hdl.handle.net/20.500.11937/23531
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author Farid, W.
McCallum, D.
Tait, Robert
Dunlop, S.
Hulse, G.
author_facet Farid, W.
McCallum, D.
Tait, Robert
Dunlop, S.
Hulse, G.
author_sort Farid, W.
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-235312017-09-13T14:00:17Z Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats Farid, W. McCallum, D. Tait, Robert Dunlop, S. Hulse, G. 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. 2009 Journal Article http://hdl.handle.net/20.500.11937/23531 10.1002/jbm.a.32283 restricted
spellingShingle Farid, W.
McCallum, D.
Tait, Robert
Dunlop, S.
Hulse, G.
Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
title Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
title_full Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
title_fullStr Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
title_full_unstemmed Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
title_short Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats
title_sort minor pathological changes are induced by naltrexone-poly(dl-lactide) implants in pregnant rats
url http://hdl.handle.net/20.500.11937/23531