Magnetic Nanocomposite Hydrogels with AC-field Induced Release as Controlled Delivery Systems for Biomedicine

Dual magnetic- and thermoresponsive-functional nanocomposites have potential in controlled release of therapeutics for biomedical applications. Such materials could act as; (i) platforms in tissue engineering or cell culture for remote-controlled delivery of growth factors/nutrients, or; (ii) as implants in cancer treatment, combining hyperthermia treatment with controlled delivery of chemotherapy drugs, negating the negative side-effects associated with current treatments. However several challenges are associated with the preparation and functionality of these materials that must be addressed before they can be applied in clinical use. In many cases the functional requirements are application-specific and materials must to be formulated on a case-by-case basis. This work focuses on the development of a dual magnetic- and thermoresponsive- nanocomposite that reduces the need for extensive modifications, in turn generating a functional material that can be utilised across a broad application range. Poly(N-isopropylmethacrylamide) (pNIPMAm) microgels display an appropriate temperature response within physiological range, hence were utilised as the thermoresponsive component in this work. A comprehensive synthetic analysis is described to characterise the physical and thermoresponsive properties of microgels formed under a range of synthetic conditions, consequently developing a set of design parameters that enable fine-tuning of these properties. Subsequently a temperature responsive bulk material, formed by incorporating pNIPMAm microgels in gelatin-based hydrogels, was evaluated as a delivery vehicle that benefits temperature stimulated drug release. Mixed gelatin type-A and type-B formulations were prepared, demonstrating advantageous properties compared to the pure gelatin hydrogels. The swelling and drug loading/release mechanisms were investigated for pure and mixed gelatin formulations to decipher the exact nature of these processes and whether they could be modulated by composition. For preparation of the magnetic component, magnetic nanoflowers (NFs) were incorporated into two different polymer materials. The hyperthermic efficiency (SAR) and physical properties were explored for a range of synthetic variables. In general SAR was retained despite immobilisation and the magnetic-gels were sufficiently stable to external conditions. Finally, the appropriate magnetic and non-magnetic components identified from this work were combined and evaluated in magnetic-field stimulated drug release. By optimising the individual components of the multi-functional material, this work has paved the way towards the rational design of versatile materials in controlled release for biomedical applications.