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

Abstract

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.

• Authors: Induvadana Ankareddi, Melissa M Bailey, Christopher S Brazel, Jane F Rasco, Ronald D Hood
• Journal: Birth defects research. Part B, Developmental and reproductive toxicology (Birth Defects Res B Dev Reprod Toxicol) Vol. 83 Issue 2 Pg. 112-6 (Apr 2008) ISSN: 1542-9741 [Electronic] United States
• PMID: 18395840 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Acrylic Resins
• Drug Carriers
• Polymers
• poly(N-isopropylacrylamide-co-acrylamide)

Topics

• Abnormalities, Drug-Induced (diagnosis)
• Acrylic Resins (chemistry, toxicity)
• Animals
• Dose-Response Relationship, Drug
• Drug Carriers (toxicity)
• Embryonic Development (drug effects)
• Female
• Fetal Resorption (chemically induced)
• Fetal Weight (drug effects)
• Male
• Maternal Exposure (adverse effects)
• Mice
• Mice, Inbred Strains
• Polymers (toxicity)
• Pregnancy
• Temperature