Abstract
Docetaxel (DTX), as a first-line anti-tumor drug, has been studied for decades for its diverse bioactivities. However, DTX presents poor solubility in water, low bioavailability and serious toxic side effects which has hindered its application in the clinic. To address these problems, docetaxel-sulfobutyl ether-β-cyclodextrin inclusion complex (DTX-SBE-β-CD) was prepared successfully by saturated aqueous solution method. Sulfobutyl ether β-cyclodetrin (SBE-β-CD) is used as delivery material. For this study, the inclusion complex of docetaxel with sulfobutyl ether β-cyclodetrin (DTX-SBE-β-CD) was prepared and optimized its properties to enhance the cytotoxicity of cancer cells. A large number of physical characterization results showed that DTX-SBE-β-CD inclusion complex was successfully prepared by saturated aqueous solution method. DTX-SBE-β-CD inclusion complex was optimized by Central Composite Design. DTX-SBE-β-CD had an inhibitory effect on the in vitro determination of MCF-7 and HepG2 cells by MTT assay. Pharmacokinetic studies were carried out on male Sprague–Dawley rats by tail injection, including the distribution, metabolism and elimination of DTX-SBE-β-CD in vivo. In the experimental study of inhibition of cancer cells, DTX and DTX-SBE-β-CD showed apparent concentration-dependent inhibitory actions on tumor cells and the inhibition of DTX-SBE-β-CD group was more obvious.
Highlights
With the invention of high-throughput screening methods, the percentage of new active molecules that are insoluble in water has risen to about 40% in total; in various therapeutic areas this percentage has even reached 80–90%
Compared with the diffractogram of pure SBE-β-CD and docetaxel, the diffraction pattern of the inclusion complex was overlapped with that of the SBE-β-CD, and obviously showed no characteristic peaks that pure docetaxel had. These results indicated that the self-lattice arrangement of docetaxel was changed from crystalline to amorphous state, which might be attributed to the docetaxel inclusion into the SBE-β-CD cavity
The results revealed that the formulation of docetaxel as a clathrate made with SBE-β-CD significantly promoted and sustained the absorption of docetaxel
Summary
With the invention of high-throughput screening methods, the percentage of new active molecules that are insoluble in water has risen to about 40% in total; in various therapeutic areas this percentage has even reached 80–90%. Those active molecules are hydrophobic compounds, which exhibit low absorption and transportion properties. Though they have high pharmacological activity, they are facing exclusion due to their low water solubility and bioavailability. Insoluble drugs should be made dissolvable by physico-chemical or biological means in order to arrive at the pharmacological target in appreciable amounts. Various approaches exemplified by the addition of co-solvents [1,2,3], solid dispersion [4], size reduction [5,6], as well as the complexation with cyclodextrins(CD) [7], have been used to optimize the solubility of insoluble substances
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
