Functionalization of microspheres with malonates using Michael Addition as a pathway to create a drug delivery system for platinum drugs for the treatment of liver cancer

Microspheres have been modified post-polymerization via Michael Addition to suit the requirement of these beads as a drug delivery carrier for platinum drugs. Ethyleneglycol dimethacrylate (EGDMA) was polymerized in a suspension system leading to microspheres with an excess of vinyl functionalities. Solid state NMR was employed to determine the amount of repeating groups with unreacted vinyl groups and a molar ratio of 28% was obtained. The percentage of vinyl groups was approximately confirmed using FT-Raman (34%). Subsequent Michael Addition of these vinyl functionalities with diethyl malonate leads to modification of almost half of the vinyl groups. Ester hydrolysis and reaction with cisplatin (cis-diammineplatinum(II) dichloride) lead to microspheres with a loading of around 9 wt% of platinum. The platinum drug was slowly released at a rate of 20% in 10 days making these microspheres suitable for the treatment of liver cancer via transarterial chemoembolization. Indeed, the drug-loaded carrier was found to be highly toxic to liver cancer cells (ATCC, HepG2) while the empty carrier is non-toxic.

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