Magnetothermally-Triggered Drug Release from Block Copolymer Micelles

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DESCRIPTION (provided by applicant): A novel approach to triggered delivery of therapeutics is proposed that will take advantage of the unique heating properties of certain magnetic nanoparticles when exposed to an AC magnetic field. The heat generated by the magnetic nanoparticles (MNPs) triggers a phase change in the host carrier, allowing the development of drug delivery systems with an external triggering mechanism. While magnetic heating (and magnetic hyperthermia) are not new subjects, the combination of these materials with temperature-responsive micelles is an innovative way to use a magnetic field to trigger release. Much of this proposal is focused on the development and careful examination of thermally-responsive systems that can be activated by a temperature increase from 37 to approximately 45 oC. By slowing (or halting) drug release until the external magnetic field is applied, the micelle-encapsulated MNP systems proposed can localize to a targeted region or cell type within the body prior to delivery of medication. This method would achieve significantly higher efficacy per drug dose than conventional strategies, and could easily be combined with magnetic fluid hyperthermia for use in cancer therapies. It provides the oncologist unprecedented control of the cancer therapy with both spatial, through cellular-level targeting, and temporal, by selecting the time and duration of the magnetic trigger. The drug carrier system is a micelle structure based on the self-assembly of diblock copolymers based on poly (ethylene oxide-co-5-caprolactone), which has a crystalline core that melts around 40-42 oC. By application of a pulsed magnetic field, heat is generated in the micelles, and as the core melts, the micelle is destabilized, causing rapid delivery of chemotherapeutic drugs. The system design allows release as the magnetic field is applied; thus, the device can be triggered by a field placed external to the patient's body. The speed and duration of the release will be investigated for different carrier parameters. To evaluate these systems for targeting and treating cancer, we will attach targeting ligands to the surface of the nano-carriers and carry out in vitro experiments on cancer and healthy cell lines. The project brings together engineers, scientists and medical researchers, and will be led by Dr. Christopher Brazel, an associate professor of chemical and biological engineering who is an expert on polymeric systems, and Dr. David Nikles, a professor of chemistry, who has significant experience with the design and characterization of magnetic nanomaterials. Dr. Joel Glasgow, an assistant professor of cardiovascular disease and human gene therapy at UAB, will lead experiments on targeting and in vitro tests in cancer cell lines. Dr. Maaike Everts, an Assistant Professor with a background in targeting vectors at UAB, will be a consultant to the research team for the targeting experiments. Dr. Jacqueline Nikles, a consultant on the project, will focus on development of block copolymers and characterizing micelle formation and disruption. PUBLIC HEALTH RELEVANCE: By developing a magnetically-triggered delivery system, more efficient therapeutic treatments can be developed. For example, micelles carrying magnetic nanoparticles can be targeted to cancer or other cells with delivery of medicine triggered by an alternating magnetic field applied outside the body. This would reduce the amount of drug required per treatment while minimizing the side effects of potent drugs. This system could have an important impact on the lives of many people seeking better treatments for a range of cancers and potentially many other medical conditions.