[Preparation of self-microemulsion drug delivery system of the mixture of paeonol and borneol based on Xingbi Fang].

The aim of this study is to prepare self-microemulsifying drug delivery system (SMEDDS) of the mixture of paeonol (Pae) and borneol (Bor). Solubility test, ternary phase diagrams and simplex lattice method were employed to screen and optimize the formulation of the mixture of Pae and Bor-loaded SMEDDS. After formed into microemulsions, the particle diameter (PD) was determined and a TEM was employed to observe the microemulsions' morphology. The contents of Pae and Bor were determined by gas chromatography. As a result, while ethyl oleate (EO) as the oil phase, cremophor EL35 (EL35) as surfactant and Transcutol HP (HP) as cosurfactant, the range of the microemulsion on the ternary phase diagram was larger than other combinations. And at a ratio of 20:45:35, the microemulsions' PD was about 34 nm and the polydispersity index (PI) was about 0.2. There were 16% of Pae, 2% of Bor, 16% of EO, 37% of EL35 and 29% of HP in the prepared SMEDDS. The preparation process of the Pae and Bor-loaded SMEDDS based on Xingbi Fang is simple and feasible. This study provides a reference for the researches on the related traditional Chinese medicine and the related components.

Development Of Novel Liposome-Encapsulated Combretastatin A4 Acylated Derivatives: Prodrug Approach For Improving Antitumor Efficacy.

PURPOSE: The objective of the present study was to develop a liposomal drug delivery system based on combretastatin A4 (CA4) prodrugs modified with varying alkyl chains and investigate the in vitro drug conversion from prodrug and in vivo antitumor effect. METHODS: The prodrug of CA4 was synthesized with stearyl chloride (18-carbon chain), palmitoyl chloride (16-carbon chain), myristoyl chloride (14-carbon chain), decanoyl chloride (10-carbon chain), and hexanoyl chloride (6-carbon chain) at the 3'-position of the CA4. Subsequently, it was encapsulated with liposomes through the thin-film evaporation method. Furthermore, the characteristics of prodrug-liposome were evaluated using in vitro drug release, conversion, and cytotoxicity assays, as well as in vivo pharmacokinetic, antitumor, and biodistribution studies. RESULTS: The liposome system with loaded CA4 derivatives was successfully developed with nano-size and electronegative particles. The rate of in vitro drug release and conversion was reduced as the fatty acid carbon chain lengthened. On the contrary, in vivo antitumor effects were improved with the enlargement of the fatty acid carbon chain. The results of the in vivo pharmacokinetic and tissue distribution studies indicated that the reduced rate of CA4 release with a long carbon chain could prolong the circulation time and increase the drug concentration in the tumor tissue. CONCLUSION: These results suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy.