In Vivo Antitumor Activity of a Novel Orally Bioavailable Ifosfamide Nanostructured Lipid Carrier Against Dalton’s Ascitic Lymphoma

Abstract

Ifosfamide is a widely used antineoplastic drug belonging to the alkylating agents. It is difficult to develop a conventional oral dosage form as it degrades in acidic media, with its rate of degradation depending on the pH of the solution. Thereby, ifosfamide is available either as a powder which is reconstituted with diluents for injection or as injectable solution. The present work has attempted to improve oral bioavailability of ifosfamide by incorporating in nanostructured lipid carriers (NLCs). The purpose of this research was to study whether the oral bioavailability of ifosfamide could be improved by administering ifosfamide-loaded NLCs. Ifosfamide NLCs were developed using chitosan cross-linking with sodium alginate by solvent diffusion technique. Bioavailability studies were conducted in albino rats after oral administration of ifosfamide suspension and NLC. In vivo antitumor activity of ifosfamide nanostructured lipid carrier against Dalton’s ascitic lymphoma (DAL) was also investigated. The results showed that the relative bioavailability of ifosfamide from NLC was increased by sixfold higher than that of ifosfamide suspension. Administration of ifosfamide NLC significantly decreased the tumor volume and viable cell count. Nonviable cell count was significantly higher in ifosfamide NLC-treated animals when compared with DAL control animals. Further, the median survival time was increased to 35 % on administration of ifosfamide NLC. Ifosfamide NLC significantly decreased biochemical parameters, increased the RBC count and Hb content, and reduced the WBC count as well. The results of this study show no significant difference in the antitumor efficacy of ifosfamide when administered as injection and nanoformulation. The obtained results are indicative of NLCs as potential carriers for improving the oral bioavailability and acid instability problems. The new nanoformulation would be interchangeable with the standard formulation.