Brain cancers such as glioblastoma multiforme are some of the most dangerous cancers with an alarmingly high mortality rate. It is reported to have the lowest survival rates at less than 20% over 5 years. There are many reasons for this but a major one is the ineffective delivery of anticancer drugs to the tumor location. This is due to the presence of certain barriers in the brain (for example, the blood-brain barrier, BBB), which protect the brain from harmful materials and also restrict the entry of useful therapeutic molecules. We undertook an investigation to develop a new non-invasive BBB targeting approach, involving the synthesis and evaluation of a range of cross-linked mikto-arm star polymers as candidates for the delivery of anticancer therapeutics across the BBB. Using the RAFT process, well-defined hydrophobic poly (butyl methacrylate) and hydrophilic poly (PEG methacrylate) arm polymers with different chain lengths were prepared. These were reacted with a dimethacrylate cross-linker to give miktoarm star polymers with particle sizes ranging from 120-300 nm. A monomeric conjugate of antineoplastic drug SN38 was prepared and incorporated into the structure during either arm synthesis or cross-linking. Thus, exploring the importance of the position of the drug molecule inside a star polymer is reported. Imaging agent, Fluorescein-o-methacrylate is incorporated into the core of the star polymer to track the polymer in different in-vitro environments. This presentation will highlight the synthetic approach to a range of mikto arm star polymer conjugates and will explore structure-property relationships such as hydrophobicity/hydrophilicity, cross-link density, and drug loading. An in vitro evaluation of the efficacy of these mikto-arm polymers to cross a BBB model system will be reported.

Core cross-linked miktoarm star polymers via RAFT polymerisation for drug delivery across biological barriers

254th National Meeting (2017)

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