A subacute toxicity study was conducted to evaluate the oral toxicity profile of
poly(N-isopropylacrylamide) (
PNIPAAm) derivatives. These thermoresponsive
polymers may have several potential
pharmaceutical applications such as ingredient for oral solid
dosage form. A preliminary acute oral toxicity study was performed with one of the
polymer (
PNIPAAm-co-NVA) at a unique dose of 4000 mg/kg
body weight administered to six male and six female mice, to determine the dosage for further evaluation. No treatment-related effect was observed on behavior and health condition of the experimental animals during the 14 days observational period. The autopsy of the treated animals did not revealed any macroscopic changes in major organ aspects. Based on these preliminary results we selected a 2000 mg/kg
body weight/day dose for the 28 days long subacute study. Three
polymers were tested, namely
PNIPAAm,
PNIPAAm-co-NVA and
PNIPAAm-co-AAc and compared to a saline control. No significant changes in clinical signs,
body weight and food consumption, hematology, clinical chemistry or absolute organ weight were observed. Histological examination of excised major organs showed no marked differences between treated and control mice. In conclusion,
PNIPAAm-co-NVA is well tolerated up to 4000 mg/kg
body weight when administered orally. In addition, the subacute study indicated the absence of cumulative toxicity and a no-observed-adverse-effect level (NOAEL) of 2000 mg/kg was identified for
PNIPAAm and its two copolymers. Further studies are mandatory.