Altered chemical and biological activities of all-trans retinoic acid incorporated in solid lipid nanoparticle powders

The principal aim of this study was to investigate whether the solid lipid nanoparticle (SLN) powder formulation of all-trans retinoic acid (ATRA) can favorably alter the chemical stability and biological activities of ATRA. SLN powder formulation of ATRA was obtained by freeze-drying of SLN dispersions. The chemical stability of ATRA was determined by HPLC analysis. The anticancer efficacy of ATRA was determined by evaluating antiproliferative effects of ATRA on cancer cell lines. Hemolytic potential of ATRA was spectrophotometrically determined after incubation with red blood cells (RBCs) in vitro. ATRA could be efficiently incorporated in SLN powder without impairing the physical stability of lipid nanoparticles. After 3 months of storage, >90% ATRA remained intact in SLN powder, indicating that the chemical stability of ATRA was substantially improved by incorporation in SLN powder. The antiproliferative effects of SLN powder formulation of ATRA on a wide range of cancer cell lines were not significantly different from that of free ATRA. Furthermore, the incorporation of ATRA in SLN powder significantly reduced the hemolytic potential of ATRA. Taken together, the molecular characteristics that currently appear to limit the clinical efficacy of ATRA were greatly improved by preparing SLN powder formulation. SLN powder formulation of ATRA may have a potential in enhancing the efficacy of ATRA in cancer chemoprevention and therapeutics. (C) 2004 Elsevier B.V. All rights reserved.