Titre du document / Document title
Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans
Auteur(s) / Author(s)
HULSE G. K. (1) ;
STALENBERG V. (1) ;
MCCALLUM D. (2) ;
SMIT W. (3) ;
O'NEIL G. (1 4) ;
MORRIS N. (1 4) ;
TAIT R. J. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Unit for Research and Education in Drugs and Alcohol, School of Psychiatry and Clinical Neurosciences (MDP 521), The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, AUSTRALIE
(2) Department of Pathology, Royal Perth Hospital, Perth WA, AUSTRALIE
(3) Clinipath Pathology, 647 Murray Street, West Perth, AUSTRALIE
(4) Australian Medical Research Foundation, AUSTRALIE
Résumé / Abstract
In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.
Revue / Journal Title
Journal of controlled release
ISSN
0168-3659
CODEN JCREEC
Source / Source
2005, vol. 108, n
o1, pp. 43-55 [13 page(s) (article)] (23 ref.)
Langue / Language
Anglais
Editeur / Publisher
Elsevier, Kidlington, ROYAUME-UNI
(1984)
(Revue)
Mots-clés anglais / English Keywords
Morphinan derivatives ;
Dosage form ;
Narcotic antagonist ;
Pharmaceutical technology ;
Biodegradability ;
Biocompatibility ;
Human ;
Implant ;
Naltrexone ;
Controlled release form ;
Lactic acid polymer ;
Mots-clés français / French Keywords
Morphinane dérivé ;
Forme pharmaceutique ;
Antagoniste analgésique narcotique ;
Technologie pharmaceutique ;
Biodégradabilité ;
Biocompatibilité ;
Homme ;
Implant ;
Naltrexone ;
Forme libération contrôlée ;
Lactique acide polymère ;
Mots-clés espagnols / Spanish Keywords
Morphinano derivado ;
Forma farmacéutica ;
Antagonista narcótico ;
Tecnología farmacéutica ;
Biodegradabilidad ;
Biocompatibilidad ;
Hombre ;
Implante ;
Naltrexona ;
Forma liberación controlada ;
Láctico ácido polímero ;
Mots-clés d'auteur / Author Keywords
Naltrexone-poly(DL-lactide) implant; Sustained release; Biocompatibility ;
Biodegradability; Humans ;
Localisation / Location
INIST-CNRS, Cote INIST : 20704, 35400013568085.0050
Nº notice refdoc (ud4) : 17247662
