| Objective:To optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and characterize the properties of this transdermal delivery system on improving the drug penetration ability through the skin.Methods:1 Optimization of the self-assembled cubic liquid crystalline nanoparticles containing paeonolThe cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein(GMO)/poloxamer 407 bulk cubic gel by heat treating method and high-pressure homogenization. After the optimization of prescription and preparation process, then have prepared the drug-loaded system.2 Investigation on the characterization and Stability of GMO-based cubic liquid crystalline nanoparticles containing paeonolBased on the best optimized formulation,we began the detect of polarized light microscope,Particle size, zeta potential,encapsulation efficiency and the investigation of differential scanning calorimetry, in order to evaluated the structure and good stability of the preparation prescription.3 The properties of this transdermal delivery system to improve the drug penetration ability in the skinIn vitro and Microdialysis studies were used to evaluated the transdermal permeation by comparing three preparations of transdermal permeation behavior within 24 hours.The per unit accumulation osmotic quantity area of the skin was calculated, and discusses the preparation of the cubic crystal nanoparticles results in targeting advantages of skin.4 The stimulating and pharmacodynamics of GMO-based self-assembled cubic liquid crystalline nanoparticles containing paeonolTo establish the influence of cubic crystal nanoparticles on pigs pigmentation models inducted Ultraviolet B,with the help of multi-functional physiological tester and HE staining to observe the skin melanin index and histopathological changes of skin. By comparing with other three preparation research,to evaluate the effect of treatment for the pharmacodynamics of preliminary research and the possible mechanism of action.Results:1. Prescription was prepared by the heat treating and high-pressure homogenization method: GMO 3.6 g, F127 0.4 g, paeonol 0.32 g and deionized water 1.2 ml, the encapsulation efficiency has exceed 90% and drug loading has exceed 2.5%. Transparent, viscous and easy daub cubic crystal nanoparticles gel of our prescription.2. The studies of Characterization indicated the wanted structures, paeonol cubosomes is nearly perfect uniform in size and evenly distributed, and the shape of the cubosomes is similar to balls, about(84.65±2.08) nm in diameter,(-33.6±0.96) m V for Zeta potential. Drug were coated in carrier and the stability of prescription is better.3. In vitro and Microdialysis studies were used to evaluated the transdermal permeation by comparing three preparations of transdermal permeation. The experiment confirmed that the paeonol cubic crystal nanoparticles can enhance the transdermal osmotic quantity significantly. The retention of paeonol cubosomes in the cuticle layer and epidermis/dermis is significantly higher than that of paeonol market ointment and ordinary gel which suggested the good targeted performance.4. The basic research of pharmacodynamics studies suggested the cubic crystal nanoparticles could improved the pigs pigmentation models, the recent curative effect is similar to the commercially available hydroquinone cream. Appearance change of stimulating experiment shows that the irritating adverse reaction is less than in hydroquinone cream and ointment.Conclusions:This study aimed to prepare and improve the transdermal drug delivery system for paeonol by using the self-assembled paeonol cubosomes which should increase bioavailability in the skin. And the irritation is smaller than that other preparations which provided a new type of treatment for the clinical treatment of inflammatory reaction and pigmentation skin disease. |
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