Developmental toxicity assessment of thermoresponsive poly(N-isopropylacrylamide-co-acrylamide) oligomers in CD-1 mice

Autor: Induvadana Ankareddi, Christopher S. Brazel, Jane F. Rasco, Ronald D. Hood, Melissa M. Bailey
Rok vydání: 2008
Předmět:
Zdroj: Birth Defects Research Part B: Developmental and Reproductive Toxicology. 83:112-116
ISSN: 1542-9741
1542-9733
DOI: 10.1002/bdrb.20150
Popis: BACKGROUND: Although polymers and hydrogels are used successfully in biomedical applications, including implants and drug delivery devices, smaller molecular weight oligomers, such as those investigated here, have not been extensively studied in vivo. Poly(N-isopropylacrylamide-co-acrylamide), or P(NIPAAm-co-AAm), has a unique thermoresponsive behavior and is under investigation as a novel drug delivery system for metastatic cancer treatment. To date, no studies have been published regarding the safety of P(NIPAAm-co-AAm) to the conceptus. METHODS: From gestation days (GD) 6–16, pregnant CD-1 mice were dosed via i.p. injection with aqueous solutions containing 500, 750, or 1,000 mg/kg/d P(NIPAAm-co-AAm). Dams were sacrificed on GD 17 and their litters were examined for abnormalities. RESULTS: P(NIPAAm-co-AAm) caused no statistically significant difference in maternal weight gain or percent resorbed or dead fetuses compared to control values, but fetal weight was significantly decreased in the two highest dosage groups. CONCLUSIONS: At the highest dosages employed, maternal exposure to P(NIPAAm-co-AAm) was associated with decreased fetal weight. However, as the estimated human exposure levels for persons using this system would be some 1,500-fold lower than the lowest dosage administered in this study, the authors feel that this oligomer was not shown to pose a biologically significant risk at relevant human dosages. Birth Defects Res (Part B), 2008. © 2008 Wiley-Liss, Inc.
Databáze: OpenAIRE