STATISTICAL OPTIMIZATION AND STABILITY STUDY OF QUERCETIN-LOADED MICROEMULSION

Objective: This research aims to develop a quercetin microemulsion system to improve the solubility of quercetin and to study the stability of the microemulsions. Methods: The microemulsion is prepared by water titration method using isopropyl myristate (oil), Tween 60®/Span 80® (3:2) (surfactant) and ethanol (co-surfactant). Two different aqueous phases, water or NaCl solution, were used to prepare microemulsions and the influence of each parameter was described. DPPH scavenging and anti-tyrosinase activity were performed along with chemical stability to evaluate the functional stability of microemulsions. Results: The influence of percentage of oil phase (variable A) on the solubility of quercetin was less significant than that of percentage of surfactant/co-surfactant (variable B). Compared to those prepared with water (variable C), the solubility of quercetin in microemulsions prepared with NaCl solution significantly increased. The ratio of the high level to low level for solubility of three variables was 1.135, 1.315 and 1.591 respectively. Increasing variable A and B led to an increase in the particle size of microemulsions from 120.08 nm to 188.38 nm and 48.18 nm to 260.28 nm, respectively. The influence of variable B was quite significant, while variable C has no significant effect on particle size. Quercetin microemulsions showed good chemical and functional stability when stored at 4 °C. Under other conditions, especially at 40 °C, the activity of the microemulsion is considerably reduced. Conclusion: The influence of different variables on the characteristics of microemulsions was complicated. Care must be taken in the composition and storage conditions of these formulations

Optimization of Formulation Parameters in Preparation of Fructus ligustri lucidi Dropping Pills by Solid Dispersion Using 23 Full Experimental Design

Oleanolic acid (OA) is an active ingredient of the traditional Chinese medicine (TCM) Fructus ligustri lucidi (FLL). Its clinical use is restricted because it is water-insoluble and has limited dosage forms of administration at present. Hence, the FFL dropping pills were prepared by the hot-melt method of solid dispersion technology. A 23 factorial design was used to examine the effects of the materials used to prepare the dropping pills (e.g., different ratios of PEG4000 and PEG6000, FLL extract loading, and percentage of Tween 80) on parameters such as dropping pill roundness, weight variation, and disintegration time. Moreover, 23 full factorial design was utilized to search for the optimal formulation for dissolution experiments. The results showed that the percentage of Tween 80 demonstrated significant effects on dropping pill roundness, weight variation, and disintegration time; FLL extract loading affected roundness and weight variation; and different ratios of PEG4000 and PEG6000 only affected disintegration time. The optimal formulation of the dropping pills released 70% of the drug after 30 min of dissolution release, which was faster than commercially available FLL Chinese medicines. Furthermore, the amount released was higher than that of commercially available formulations. In this study, a solid dispersion technique was used to successfully produce FLL dropping pills. In addition to improving the water insolubility of FLL and increasing the dissolution release percentage of the drug, we increased the application value of FLL and reduced the issues of traditional administration dosage forms

Brk Activates Rac1 and Promotes Cell Migration and Invasion by Phosphorylating Paxillin

Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a human metastatic breast tumor, and its overexpression is frequently observed in breast cancer and several other cancer types. However, the molecular mechanism by which this kinase participates in tumorigenesis remains poorly characterized. In the present study, we not only identified paxillin as the binding partner and substrate of Brk but also discovered a novel signaling pathway by which Brk mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show that EGF stimulation activates the catalytic activity of Brk, which in turn phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the activation of small GTPase Rac1 via the function of CrkII. Through this pathway, Brk is capable of promoting cell motility and invasion and functions as a mediator of EGF-induced migration and invasion. In accordance with these functional roles, Brk translocates to membrane ruffles, where it colocalizes with paxillin during cell migration. Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy