Multifunctional polymeric micelles via RAFT polymerization for efficient drug delivery

Abstract

The objective of this thesis is to investigate the applicability of reversible addition fragmentation chain transfer (RAFT) polymerization technique to the synthesis of well-defined, biocompatible, and stable polymeric micelles that can be used for drug delivery. To achieve this aim, various polymeric micelle systems based on different amphiphilic block copolymers have been prepared and intensively investigated. Poly(ethylene glycol) methyl ether methacrylate, which is closely related to poly(ethylene oxide) in biocompatibility and low-fouling properties was chosen as a hydrophilic building block. Different strategies were employed to stabilize the core of the prepared micelles. The hydrophobic block was introduced with isocyanate reactive anchors for difunctional amine groups of the cross-linker to generate core cross-linked micelles. Alternatively, the micelles with RAFT endgroup located in the core were cross-linked using divinylbenzene cross-linker. The prepared platinum(IV) drug was incorporated into the polymer backbone while simultaneously cross-linked the core of the micellar structures. The reduction of platinum(IV) complexes in the core of the micelles in the reductive environment led not only to the release of reactive cisplatin but also to cleavage of the cross-linker to form free block copolymer and therefore, facilitates the excretion from the body. The micelles were decorated with RGD containing peptide to enhance the cell uptake. The in vitro study revealed the promising antitumour activity of platinum(IV) incorporated into the prepared micellar structure and the better properties of cross-linked micelles conjugated with peptide, as drug carriers compared with uncross-linked micelles.