Study On New Types Of Retinoic Acid Based On Nanotechnique

Retinoic acid (RA), a lipophilic derivative of vitamin A, is known to be effective to prevent proliferative vitreoretinopathy (PVR). In this paper , RA nanosuspension, RA solid lipid nanoparticle (RA-SLN) and RA nanostructured lipid carrier (RA-NLC) were prepared and characterized. The major contributions include the following aspects:Preparation, characterization and animal experiment of RA nanosuspensionRA nanosuspensions with different concentrations were prepared by solvent-diffusion method in aqueous and freeze-drying. The mean particle size before and after drying was determined by photon correlation spectroscopy (PCS) method and the morphology of RA nanoparticles was characterized by transmission electron microscope (TEM). The concentrations of all-trans retinoic acid (ATRA) in different time were measured by high performance liquid chromatography (HPLC) method to analyze drug loading and stability. The results show that the mean diameter of RA nanoparticles (RA-NP) falls into the 200-400nm. Drug loading of the system is 35mg/L. It is demonstrated that the concentration of ATRA can be kept in the range of effective antiproliferation for 4 weeks, which indicates that RA nanosuspension has effectively prolonged the drug release time. Preparation and characterization of RA-SLNRA-SLN was prepared by solvent-diffusion method in aqueous system. The mean particle size and zeta potential were decided by PCS method and zeta potential analyzer. Its morphology was examined by TEM. The concentrations of all-trans retinoic acid(ATRA) for different time density were determined by high performance liquid chromatography(HPLC) method. Results: The mean diameter of RA-SLN is from 300nm to 400nm for the different lipid, zeta potential is from –28mV to –40mV, drug loading is 15mg/L. Within 4 weeks, the concentration of ATRA is in the range of effective antiproliferation, prolong the drug release time. Preparation and characterization of RA-NLCThe nanostructured lipid carriers (NLC) loaded with retinoic acid (RA) were prepared by high pressure homogenization and characterized by transmission electronic microscope (TEM), particle size analyzer, zeta potential analyzer and high-performance liquid chromatography (HPLC). The results show that when the homogenization cycle number vary from 1 to 12, the mean particle size decreases from 120 nm to 10 nm, while polydispersity indices (P.I.) increases from 0.26 to 0.69. The concentration of RA loaded can reach 56.26 mg/L and the stability of RA is improved in NLC so that the required concentration of RA can keep for a long time. As far as stability of NLC is concerned, its zeta potential is -30.9±0.6mV and it remains stable after 120 min centrifugation (4℃, 10000 r/min) or 1 year storage avoiding light. Besides, Freeze-drying can also be used to store it longer.