CuiFang Cai

Name: 蔡翠芳

Organization: Shenyang Pharmaceutical University , China

Department:

Title: Associate Professor(PhD)

Chemicals
References

Effects of Pluronic F127-PEG multi-gel-core on the release profile and pharmacodynamics of Exenatide loaded in PLGA microspheres

Co-reporter:Puxiu Wang, Qian Wang, Tianyang Ren, Haoyu Gong, Jingxin Gou, Yu Zhang, Cuifang Cai, Xing Tang

Colloids and Surfaces B: Biointerfaces 2016 Volume 147() pp:360-367

Publication Date(Web):1 November 2016

DOI:10.1016/j.colsurfb.2016.08.032

•Pluronic—PEG multi-gel-core was used to prepare PLGA microsphere and store drug.•Exenatide was located at the hydrophilic domain of F127-PEG.•The biological activity of drug was protected by multi-gel-core structure.•The drug release is controlled by both PLGA and multi-gel-core.Pluronic F127 and PEG as a multi-gel-core were used to prepare Exenatide-loaded microspheres and store the drug within the microspheres. Also, the sol-gel transition and novel functions of the Pluronic F127-PEG gel core were investigated.Microspheres with a multi-gel-core (GCMs) and without a multi-gel-core (Ms) were compared in terms of the rate of PLGA degradation, therelease kinetics in vitro and the efficacy in KKAy mice. The drug release of GCMs was at a constant rate, and slower than Ms. In addition, after the KKAy mice were given Exenatide for 55 days, the blood glucose concentration and HbA1c concentration in the GCMs group were lower than that in the Ms group. The obtained results demonstrated that a single injection of GCMs allowed the mice to maintain a stable blood glucose concentration for two weeks and their body weight was reduced more effectively than that in the Ms group. In addition, GCMs had a longer interval between dosing (two weeks) and a lower dosage(2.4 μg/kg) than Bydureon® (one week, 33 μg/kg). The bioactivity and release of macromolecular Exenatide was improved by the multi-gel-core structure:(1)The hydrophilic Exenatide tended to partition into the PEG chains of F127 and PEG homopolymer, and so it was protected from the organic solvent and vigorous stirring; (2)The macromolecular Exenatide was released both by diffusing through the hydrophilic F127-PEG chains and hydrophobic PLGA.

Preformulation and development of chemically stable lipid emulsions containing a novel taxane derivative, TM-2

Co-reporter:Jianli Shi;Xi Chen;Yuechen Gu;Xi Hu;Ling Zhang;Yan Li;Xing Tang

European Journal of Lipid Science and Technology 2014 Volume 116( Issue 4) pp:486-496

Publication Date(Web):

DOI:10.1002/ejlt.201300371

Abstract

TM-2 is a novel taxane derivative. The present paper describes an investigation of the physicochemical properties and degradation kinetics of TM-2 to determine the use of lipid emulsions as suitable drug carriers, and also to develop and evaluate a highly stable and sterile optimal formulation of a TM-2 lipid emulsion (TLE). The properties of TM-2, such as its solubility in water and oils, partition coefficient, stability in aqueous solutions and oils, indicated that TM-2 was an excellent candidate for o/w emulsions. A preformulation study indicated that degradation of TM-2 took place mostly in water compared with that in oils. Moreover, the influence of pH, temperature, and ionic strength on the stability of TM-2 in water solutions was assessed. An emulsion formulation of TM-2 which was stable enough to undergo sterilization was successfully developed. Using the Arrhenius equation, the shelf-life of TM-2 in lipid emulsion was estimated to be 2665.5 days at 4°C, which was much longer than that of 113.0 days in aqueous solution. Thus, TLE was clearly superior to the TM-2 aqueous solution in terms of stability. Short-term stability investigations showed that the TLE was stable for a period of 3 months at 4 and 25°C.

Practical applications: The application of taxanes in anti-cancer field is limited by de novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxic agents. TM-2 is a novel semi-synthetic taxane derivative, which can overcome multidrug resistance. Some non-ionic surfactants, such as Cremophor EL and Tween 80 (polysorbate 80), usually used in the commercial formulations of the taxanes to improve their poor water-solubility, have exhibited serious adverse effects including hypersensitivity reactions and peripheral neuropathy in human. In this study, preformulation study showed that TM-2 exhibited excellent solubility in oils and, thus, the problems associated with the poor solubility of TM-2 were overcome by loading TM-2 into the interior oil phase of o/w lipid emulsions. According to the degradation kinetics results, the shelf lives (T_0.9) of TM-2 lipid emulsions at 25 and 4°C were dramatically prolonged.