Pharmacokinetics and therapeutic efficiency of a novel cationic liposome nano-formulated all trans retinoic acid in lung cancer mice model

Purpose: The externally given all trans retinoic acid (ATRA) for the treatment of certain solid cancers faces challenges such as stability, persistence, and effective targeted delivery into cell which necessitate the development of a suitable liposomal formulation for ATRA treatment. Methods: Lipo-ATRA was developed using 1, 2- Dioleoyl-3-trimethylammonium-propane (DOTAP), cholesterol and ATRA (70:20:10) by dry thin film method and investigated for its in vitro characteristics, in vivo ATRA bioavailability and pharmacokinetic properties in normal and cancer mice using HPLC. The in vivo therapeutic efficiency of lipo-ATRA was also studied. Results: DOTAP lipo-ATRA (91.676 +/- 1.29%) of 262.776 +/- 1.045 d nm size with smooth spherical surface was developed which was stable at up to 60 days with sustained ATRA release through dialysis membrane. The serum pharmacokinetics for lipo-ATRA in cancer bearing mice has shown a higherhalf-life-(14.8200h), C-max (0.66 mu g/ml) and a lower CL (46.6061 mu g/ml/h) in vivo when compared with free ATRA group (t(1/2)-13.2205h, C-max-0.29 mu g/ml, CL-136.2725 mu g/ml/h). A significantly higher bioavailability in blood and lung even after 24 h with a promising therapeutic efficiency was observed in lipo-ATRA group. Conclusions: The results showed that the formulation of lipo-ATRA in DOTAP and cholesterol in the ratio of 70:20 was the suitable carrier for ATRA in treating lung cancer. (C) 2017 Elsevier B.V. All rights reserved.