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

Altered chemical and biological activities of all-trans retinoic acid incorporated in solid lipid nanoparticle powders
November 2004
Soo-Jeong Lima, Mi-Kyung Leeb and Chong-Kook Kimb,
aResearch Institute, National Cancer Center, Goyang, Gyeonggi, Korea
bNational Research Lab for Drug and Gene Carriers, College of Pharmacy, Seoul National University, Korea
Journal of Controlled Release Volume 100, Issue 1 , 5 November 2004, Pages 53-61
Received 22 September 2003; accepted 27 July 2004. Available online 18 September 2004.
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Abstract
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.