Abstract
DESIGN AND SYNTHESIS OF NEW POLYETHYLENE GLYCOL-HYALURONIC ACID-MELPHALAN (PEG-HA-MEL) AS A TARGETED ANTITUMOR DRUG

Xiao-Ye Jiang, Xuan Wang and Qi-Xiong Li*

ABSTRACT

Background and aims: Melphalan (MEL) is a non-target selective anticancer agent with a short plasma half-life. The objective of the current study was to design targeted delivery and extend plasma half-life of MEL so as to enable it to play a better antitumor role. Methods: Polyethylene glycol-Hyaluronic acid (PEG- HA) was obtained by modifying Hyaluronic acid (HA) with activated PEG. PEG-HA was then connected with MEL to prepare the PEG-HA-MEL prodrug. The prodrug generates micelles by self-assembly in aqueous solution, and was characterized by nuclear magnetic resonance and infrared spectroscopy. Changes of tumor cell morphology and cytotoxicity were observed by an inverted microscope. Results: In this study, the PEG-HA-MEL prodrug was synthesized by PEG-HA connected with MEL. Dynamic light scattering (DLS) and transmission electron microscope (TEM) showed that the prodrug formed micelle and was evenly distributed in 100-130nm. Tumor cells treated with PEG-HA-MEL (10−6 mol/L) were condensed and rounded, aggregated into clumps, and the number of cells was significantly reduced at 24 hr and 48 hr after treatment, respectively. Conclusion: By connecting PEG-HA with MEL, it was found that this compound played a potent inhibitory role on tumor cells. This is a new method for the synthesis of PEG-HA-MEL prodrugs as targeted antitumor therapy.

Keywords: Melphalan, Polyethylene glycol - Hyaluronic acid, Hyaluronic acid, Synthesis, Antitumor.


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