Injectable Supramolecular Hydrogel Fabricated By Doxorubicin Prodrug And α-Cyclodextrin For PH-Triggered Drug Release

With the rapid development of biomaterials, more efficient drug release systems have drawn immense attentions in recent years. The innovative design of drug carrier and the ways of controlled drug release have gradually become the research hotspots. The molecule drugs are conjugated to the polymer to give the prodrug, which can signigicantly increase the water solubility, improve the utlilization and decrease the side effects of the durgs. The hydrogels become promising biomaterials with their the pronous structure to encapsualte bioactive agents, such as drugs, proteins, genes, and even living cells. Herein,we present a facile method to fabricate supramolecular hydrogels via host-guest interaction between PEG chain and α-cyclodextrin(α-CD). The main contents of the thesis are listed as follows:Part I. Injectable supramolecular hydrogel fabricated by PEGylated doxorubicin prodrug and α-Cyclodextrin for pH-triggered drug releaseWe herein report on the synthesis and characterization of a supramolecular hydrogel, which was formed by host-guest interaction between α-CD and a PEGylated doxorubicin prodrug linked with an acid-cleavable hydrazone group(mPEG-Hyd-DOX). The host-guest interaction was demostrated by X-ray diffraction(XRD) analysis. The structure and morphology of the supramolecular hydrogels were systematically investigated by differential scanning calorimetry(DSC), scanning electron microscopy(SEM) and thermogravimetric analysis(TGA). The sol-gel transition process was monitored by dynamic and steady rheological analysis. The results of pH-responsive property, in vitro cytotoxicity and drug release revealed that this kind of supramolecular hydrogel can be used as a potential injectable matrix for the encapsulation and controlled release of hydrophobic anticancer drugs. On the other hand, other therapeutic agents could be loaded into the hydrogel matrix by simple premixing. This study also provides an alternative for the construction of dual- or multi-drug delivery systems.Part II. Injectable supramolecular hydrogel fabricated by polyphosphoester prodrug grafted with PEG chain and α-Cyclodextrin for pH-triggered drug releaseA novel polyphosphoester doxorubicin prodrug(PBYP-g-PEG-g-DOX) have been synthesized via ring opening polymerization of 2-(but-3-yn-1-yloxy)-2-oxo-1, 3, 2-dioxaphospholane(BYP) and CuAAC “Click”. 1H NMR, 13 C NMR, 31 P NMR, FT IR and Gel Permeation Chromatography(GPC) were applied to characterize the compositions and structures, which indicated that the polyphosphoester doxorubicin prodrug was obtained successfully. Subsequently, the obtained polyphosphoester doxorubicin prodrug interacted with α-CD to form the supramolecular hydrogel because of its side PEG chain. The host-guest interaction was demostrated by XRD analysis. The structure and morphology of the supramolecular hydrogel were systematically investigated by DSC, SEM. Dynamic and steady rheological analysis monitors the sol-gel transition. MTT assay was employed to confirm the favourable biocompatibility and low cytotoxity of the supramolecular hydrogel. The results of pH-responsive property and drug release revealed that this kind of supramolecular hydrogel can be used as a potential injectable matrix for the encapsulation and controlled release of hydrophobic anticancer drugs.