DRUG DELIVERY SYSTEM · Collaborative Mathematical Research Applicable To Martensitic Micro-devices And Their Use For The Design Of The Open Loop Targeted Drug Delivery Systems

Final Activity Report Summary - DRUG DELIVERY SYSTEM (Collaborative mathematical research applicable to martensitic micro-devices and their use for the design of ... drug delivery systems)

The project area has been "nano-health/cancer nano-technology" that strives to ultimately allow detection of human tumours at the very earliest stages, regardless of the location of the primary tumour and/or metastases. This activity aspires to provide approaches to more effectively destroy tumours as well as their associated vascular supplies with fewer adverse side effects. The project addressed the design and evaluation of functionalised nano-composite capsules with imbedded magnetic shape memory (MSM) nano-rods formed by a brittle xerogel acting as a delivery system with drug molecules incorporated into the capsule's fractal-like structure. The surface of the nano-capsules is functionalised for a spot delivery into the tumour cells. The nano-composite xerogel matrix is synthesised to be able to carry potent drugs that can be released upon remote activation by a moderate magnetic field generated by, e.g., the magnetic resonance imaging (MRI). The activation mechanism is based on a phase transition induced by the strain-external magnetic field hysteresis of the nano-rods. This novel application of a unique physical phenomenon allows for a truly programmable, drug independent, open loop, targeted delivery system exploiting the convergence of nano-scale material science, chemistry, cancer biology, pharmacokinetics and mathematics. The fundamental outcomes of the project are threefold: Development of a breakthrough bio-MEMS random nano-composite material based on the ferromagnetic shape memory nano-rods imbedded in a fractal xerogel structure holding an incompressible liquid. This material system is scalable up to 40nm while its responsiveness to the actuation by an external magnetic field of 1.5T is maintained. The delivered nano-technology belongs into a novel group of the active drug carriers using various phase transitions as the actuating/release trigger. The nanotechnology shares a common physical underpinning: a phase transition phenomenon. But unlike available systems it is not limited to e.g. changing light into heat but it changes magnetic energy into mechanical work. This is by far more generic. It allows for a desired freedom in the design, timing, release profile and the choice of pharmaceuticals for a delivery strategy. Binding of specific markers to the surface of such a delivery system allows for controlled and targeted delivery. Development of a mathematical theory of nano-transport of tissues. The theory of motion of nano-particles addresses the question of motion of sub-micron particles in tissues, complex bio-environments, and, specifically, in tumours. This area is profoundly connected with application of any drug-carrying devices or imaging particles used in the area called "nano-medicine". The deep understanding of nano-particles transport plugs certain branches of nano-medicine for a long time. The developed theory provides a model that can be used to answer to the question of a possibility to deliver nano-particles to tumor tissues. One particular output of the theory based on large-scale simulations predicts that even radioactively labelled albumin (the best case scenario nano-particles) cannot be used to image stage four metastasis. The interoperation of this result is that, in general, the cancer is not curable under adverse circumstances. It should be strongly emphasise that it is preventable and curable at early stages. Development of the Interfacial spectral theory. This novel theory addresses elliptic problems with internal (immersed) constraints. We have been developing this theory for about two years. Nevertheless the fundamental building blog needed, the compactness of the interfacial trace operator, has been escaping us for a quite some time. The proof of this result that generalises Sobolev imbedding theory was accomplished in collaboration with R. M. Hard and V. Mazya. There are two immediate applications of this theory that find their targets: (1) Nano-fluidic encapsulation that has been contractually licensed to DeBioPharm, S.A., and (2) the charge distribution due to lightning used by 'National centre for atmospheric research' (NCAR) in the US.

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