Figure 5. Release of Propofol versus time of prodrug 2f, 3e, 3f in SD rat plasma.
In this study, we have developed some novel M-PEGs modified Propofol prodrugs from which promising anesthetic candidate was
identified. Monodispersity of PEGs is usually a minor or negligible factor in the safety and efficacy of PEGylated drugs. Therefore,
polydisperse PEGs are overwhelmingly used in pharmaceutical industry and biomedical research. In this work, the high value of
monodisperse oligoethylene glycol was illustrated not only by the high purity of M-PEGs modified Propofol prodrug, but also by fine-
tuning of the water solubility, biocompatibility, and anesthetic efficacy through accurately monitoring the length of M-PEGs. More
importantly, M-PEGs modified Propofol prodrug successfully avoided the low water solubility and complicated formulation issues of
Propofol and achieved high biocompatibility and therapeutic efficacy. Beside highly charged Propofol prodrugs like Fospropofol, these
none-charged Propofol prodrugs may be promising candidate for clinical application.
Acknowledgements
We are thankful for financial support from the National Key Research and Development Program of China (2016YFC1304704), the
National Natural Science Foundation of China (21572168), and State Key Laboratory for Magnetic Resonance and Atomic and
Molecular Physics (Wuhan Institute of Physics and Mathematics).
Supplementary material
Supplementary data associated with this article can be found, in the online version, at http://
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Highlights
Prodrugs to overcome major drawbacks of existing drug