Studies On The Solid Lipid Nanoparticles Loaded With All-trans Retinoic Acid

Solid lipid nanoparticles (SLN) is a promising drug delivery system with solid lipid as drug carriers, diameters ranging between 50 and 1000 nanometers, which has the advantages of high physical stability, slow speed of drug leakage and low toxicity etc. The objective of this thesis was to study the preparation, characterization, in vitro release and in vivo behavior of SLN with all-trans retinoic acid (ATRA) as a model drug.An HPLC method with methanol-0.05mol/LNH4H₂PO₄(90/10, v/v) as mobile phase was developed for the assay of ATRA in formulation, solubility and oil/water partition coefficient of ATRA. The analysis method was precise, simple and reliable. Solubility of ATRA showed that it was almost insoluble in water. Partition coefficient results showed that it was highly lipophilic as the model drug for the preparation of SLN.According to the results of the pre-formulation study, ultrasonic-hot pressure homogenization method was developed to prepare ATRA-SLN dispersion, ultrasonic time and intensity, homogenization cycle and pressure were key factors for the preparation of SLN. A high drug loading SLN could be acquired with Compritol 888 ATO as lipid carrier, Soybean lecithin/Pluronic F₆₈ (or Soybean lecithin/Tween 80) as emulsifiers. Base on the study above, with the criteria of encapsulation efficiency and long-term stability, orthogonal design experiments were performed to optimize the process parameters.Many physico-chemical characteristics of ATRA-SLN were investigated. The appearance and particle size distributions of the ATRA-SLN were examined by transmission electron microscopy and photon correlation spectroscopy (PCS), respectively. The dynamic dialysis was performed to investigate the in vitro release; the drug entrapment efficiency (EE) was measured by HPLC after ultracentrifugation and the drug loading capacity and pattern, the long-term stability were also evaluated.The appearance of SLN was spheric with mean particle size of (89.3 ±11.2) nm and (158.3 ± 8.7) nm for Tween-SLN and F₆₈-SLN, respectively. The ζ potential and pH of the ATRA-SLN were detected to be -30 -40 mV and 5.8⁵.9. The encapsulation efficiency was above 90 %. Results of the release experiments indicated that the release rate of ATRA from...