Preparation And Evaluation Of Liposome From Scutellaria Baicalensis Total Flavonoids

Scutellaria baicalensis Total flavonoid (STF) is a flavonoid compound extracted from the dry root of scutellaria, mainly including baicalin, baicalein and Wogonin, etc. It is reported that it has antipyretic, anti-inflammatory, protect liver, anti-virus, anti-oxidation, anti-tumor and many other pharmacological properties. At present, radix scutellariae flavonoids listed agents, oral bioavailabiliry are low, the lack of tissue targeting. Therefore, this study intends to develop a novel STF-loaded liposome (L-STF), trying to improve the performance of the absorption and distribution of effective components from the existing formulations, improve the bioavailability of drugs and targeting of liver, spleen, lungs. The main contents and results are as follows:1. Before prescribing research:Establishing the ultraviolet measurement method about the STF contained in L-STF. Studying its physical/chemical properties and stability. Establishing the quality evaluation index. The results showed that the method conforming to the requirements of the measurement, could be used for the determination of STF. The performance of solubility and stability of STF in pH 7.0 phosphate buffer solubility was superior. And the oil-water partition coefficient 1gP was-0.726 in this condition. The evaluation index of the optimization process of the liposome was determined by the appearance of the characters and the encapsulation efficiency.2. Preparation technology research:Using single factor experiment to confirm the liposome prepared by reverse evaporation method, and through the Box-Behnken Design (BBD) and the orthogonal experiment to ascertain the prescription of liposomes were as follows:Phospholipid concentration was 30 mg/mL; Bile lipid ratio was 3:1; Oil-water ratio was 2:1 and the drug concentration was 5 mg/mL. The technics were:Hydration temperature was 45?; Hydration time was 40 min; Ultrasonic time and speed were 10 min and 40 r/min, respectively. Validation and amplification experiments showed that the liposomes prepared by this prescription and process had good appearance and the encapsulation efficiency was 87.08%.3. Quality evaluation study:The results showed that the three batch of liposomes were uniform suspension with faint yellow color. Its appearance was round, and the internal structure was "fingerprint-shape". It was found that the size and the electric potential were (160.7±12) nm and (-41.4±2.3) mV. The encapsulation efficiency was over 85%and the drug loading was about 5.3%. The stability was good at 4?, avoiding light preservation. In-vitro drug release results showed that the STF was encapsulated by liposomes, which had a certain slow-release effect and was in accordance with Weibull equation.4. In-vitro anti-tumor effect:F-STF and L-STF had a certain influence on the growth and the migration of A549, MCF-7, HepG2 and HCT116 cells, showing dose/time-dependent manners. The cell growth and migration of liposome group was significantly stronger in comparison to the other group which was not encapsulated by liposomes (P< 0.01, P< 0.05). And the blank liposomes had no effect on cell growth and migration (P> 0.05).5. Pharmacokinetic study:Establishing a method for determination of baicalin content inplasma and tissues. Rats were total flavonoids 0.5% CMC-Na suspension and total flavonoids liposome.The result showed that the curves of two groups of baicalin concentration related to time showed double-peaks. Liposome group (Tmaxl and Tmax2) retarded from 0.5 h to 2 h and 8 h to 10 h respectively compared to the suspension group. AUC(o-t),AUC (0-?),MRT(0-t) and Cmax significantly increased (P< 0.01), which were 2.782, 2.711 and 1.033 times of suspension group. WhileVz/F and CLz/F were reduced by 2.942 and 2.725 times (P< 0.01), indicating that liposomes could prolong the action time of drug in vivo and have a certain slow release function. This notablely improves the oral bioavailability of the drugs. Additionally, the results of tissue distribution showed that liver, spleen, lung targeting enhanced while the drugs loaded by liposomes. This study provided a certain experimental basis for the improvement, development and application of the Scutellaria baicalensis total flavonoids formulation.