Abstract
In this study, we report the synthesis and characterisation of a thermogelling poly(carbonate urethane) system comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG) and poly(polytetrahydrofuran carbonate) (PTHF carbonate). The incorporation of PTHF carbonate allowed for the control of the lower critical solution temperature (LCST) and decreased critical gelation concentration (CGC) of the thermogels significantly. In addition, the as-prepared thermogels displayed low toxicity against HepG2, L02 and HEK293T cells. Drug release studies were carried out using doxorubicin (Dox). Studies conducted using nude mice models with hepatocellular carcinoma revealed that the Dox-loaded poly(PEG/PPG/PTHF carbonate urethane) thermogels showed excellent in vivo anti-tumour performance and effectively inhibited tumour growth in the tested model.
Highlights
Hydrogels are hydrophilic three-dimensional polymeric networks that hold a significant amount of water but do not dissolve in excess amounts of water due to the presence of physical, chemical or supramolecular crosslinks [1,2,3,4,5]
Random multi-block poly(PEG/PPG/PTHF carbonate urethane) copolymers were produced by Random multi-block poly(PEG/PPG/PTHF carbonate urethane) copolymers were produced by reacting diols of poly(ethylene glycol) (PEG), PPG and PTHF carbonate of various weight ratios, using hexamethylene diisocyanate (HDI) as a coupling reacting diols of PEG, PPG and PTHF carbonate of various weight ratios, using HDI as a coupling reagent and and dibutyltin dilaurate catalyst.TheThe synthesis process is illustrated reagent dibutyltin dilaurate as as a a catalyst
Chemical structures and molecular characteristics of the copolymers were studied by Gel permeation chromatography (GPC) and 1H
Summary
Hydrogels are hydrophilic three-dimensional polymeric networks that hold a significant amount of water but do not dissolve in excess amounts of water due to the presence of physical, chemical or supramolecular crosslinks [1,2,3,4,5]. Polymers 2018, 10, 89 sol-to-gel transition when exposed to a temperature change Such characteristics are advantageous for biomedical applications, like thermogels, that may be administered using a simple syringe delivery, undergoing in-situ gelation at physiological temperature to form a local depot for the delivery of drugs and therapeutics [20,21,22]. The local administration of a stimuli-responsive drug depot with reasonable sustained release properties, such as a drug-loaded thermogel, could serve as a better option for the elimination of primary tumours In this contribution, we design a new urethane-based thermogelling system by integrating poly(polytetrahydrofuran carbonate) (PTHF carbonate) with biocompatible PEG and PPG. In order to further understand the potential of this newly developed thermogel as an in vivo drug reservoir, we demonstrate the release of anti-cancer drugs for the effective inhibition of tumour growth for potential applications in anti-cancer therapy
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