International Journal of Pharmaceutics 2002-08-28

Formulation parameters determining the physicochemical characteristics of solid lipid nanoparticles loaded with all-trans retinoic acid.

Soo-Jeong Lim, Chong-Kook Kim

Index: Int. J. Pharm. 243(1-2) , 135-46, (2002)

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Abstract

Solid lipid nanoparticles (SLNs) have gained attention as a colloidal drug carrier, particularly for drugs with limited solubility. The poor aqueous solubility of all-trans retinoic acid (ATRA) has been a limiting factor in its clinical use. This study was undertaken to overcome the solubility limitation of ATRA by loading in SLNs. The physicochemical characteristics of ATRA-loaded SLNs were investigated by particle size analysis, zeta potential measurement, thermal analysis and HPLC determination of ATRA content. The mean particle size of ATRA-loaded SLNs could be reduced (1) by mixing EggPC and Tween 80 as a surfactant and (2) by increasing the total surfactant amount. The smallest mean particle size of SLNs was obtained with 50 mg/g surfactant mixture composed of 54:46% (w/w) EggPC:Tween 80 (154.9 nm). The zeta potential of SLNs could be increased by mixing EggPC, Tween 80 and DSPE-PEG in the surfactant mixture. The zeta potential of SLNs prepared with 50 mg/g surfactant mixture composed of 48:6:46% (w/w) of EggPC:DSPE-PEG:Tween 80 was -38.18 mV. ATRA could be loaded at 2.4% (percentage of lipid matrix) on these SLNs without impairing their physical stability. After freeze-drying, the mean particle size and polydispersity index of ATRA-loaded SLNs were only slightly increased (181.8 vs. 265.2 nm, 0.173 vs. 0.200). Furthermore, no significant change was observed in the SLN-loaded concentration of ATRA and the zeta potential of SLNs after freeze-drying. Taken together, SLN formulation of ATRA with similar characteristics to those of parenteral emulsions could be obtained even after freeze-drying.Copyright 2002 Elsevier Science B.V.