Abstract: The invention relates to microbubble complexes for use in methods of sonodynamic therapy which comprise a microbubble attached to or otherwise associated with one or more linking groups, each linking group being bound to at least one sonosensitising agent and at least one chemotherapeutic agent. It further relates to the microbubble complexes themselves and to pharmaceutical compositions which contain them. The invention is particularly suitable for the treatment of deep-sited tumors, in particular pancreatic cancer.

Abstract: The invention relates to a microbubble-chemotherapeutic agent complex comprising a microbubble carrying a combination of chemotherapeutic agents for use in a method of treating cancer in a patient, wherein said combination of chemotherapeutic agents comprises: (a) a 5-fluoropyrimidine or a derivative thereof; (b) irinotecan or a derivative thereof; and (c) a platinum-based chemotherapeutic agent or a derivative thereof; and wherein said method comprises simultaneous, separate or sequential administration of folinic acid or a derivative thereof. The invention is particularly suitable for use in the treatment of deep-sited tumours and associated metastatic disease, for example in the treatment of pancreatic cancer. The invention further relates to the microbubble- chemotherapeutic agent complexes themselves, to methods for their preparation and to pharmaceutical compositions which contain them, optionally in combination with folinic acid or a folinic acid derivative.

Abstract: The invention provides polymeric particles comprising a matrix of a biocompatible polymer and polyethylene imine, said matrix having incorporated therein an anionic or hydrophobic sonosensitiser and, optionally, an immunomodulatory agent and/or an imaging agent. Such particles find use in methods of sonodynamic therapy, in particular in methods of combined sonodynamic therapy and immunotherapy, for example in the treatment of cancer, metastasis or micrometastasis derived from cancer. The invention is particularly suitable for the treatment of deep-sited, hard to treat tumours such as pancreatic cancer.

Abstract: The invention relates to methods of sonodynamic therapy comprising the co-administration of a microbubble-chemotherapeutic agent complex together with a microbubble-sonosensitiser complex. It further relates to pharmaceutical compositions comprising these complexes and their use in methods of sonodynamic therapy and/or sonodynamic diagnosis. Such methods find particular use in the treatment of cancer, e.g. pancreatic cancer.

Abstract: The invention provides a method of preparing a microbubble covalently attached to at least one therapeutic agent which comprises: (i) providing a lipid (e.g. a phospholipid) capable of forming a microbubble; covalently linking at least one therapeutic agent to said lipid to produce a functionalised lipid; and preparing a microbubble from said functionalised lipid. Microbubble-therapeutic agent complexes which comprise a microbubble shell formed from a plurality of lipids (e.g. phospholipids) in which at least a proportion of the lipids are covalently linked to at least one therapeutic agent are also provided. Examples of therapeutic agents which may be attached to the microbubble include chemotherapeutic agents and sonosensitising agents. The complexes find use in methods of sonodynamic therapy and, in particular, in methods of combined sonodynamic therapy and chemotherapy.

Abstract: The invention relates to methods of sonodynamic therapy comprising the co-administration of a microbubble-chemotherapeutic agent complex together with a microbubble-sonosensitiser complex. It further relates to pharmaceutical compositions comprising these complexes and their use in methods of sonodynamic therapy and/or sonodynamic diagnosis. Such methods find particular use in the treatment of cancer, e.g. pancreatic cancer.

Abstract: The invention generally relates to sonodynamic therapy using microbubble-sonosensitiser complexes and, more specifically, to such therapy for the treatment of deeply-sited tumours and associated metastatic disease. In particular, the invention relates to a combination therapy in which sonodynamic treatment of deeply-sited tumours with microbubble-sonosensitiser complexes is combined with treatment using immune checkpoint inhibitors. It further relates to methods of sonodynamic therapy in which a sonodynamic-induced abscopal response modulates a systemic regression of metastatic disease. In such methods the abscopal response may be further enhanced by co-administration of an immune checkpoint inhibitor. The invention is particularly suitable for the treatment of pancreatic cancer (e.g. pancreatic ductal adenocarcinoma) and associated metastasis.

Abstract: The invention provides CaO2 nanoparticles having a pH-responsive coating for use in a method of adjuvant therapy of hypoxic tumour cells or tissues. The nanoparticles find particular use in enhancing cancer therapies that depend on oxygen to exert their effect, such as photodynamic therapy (PDT), sonodynamic therapy (SDT), and radiotherapy. The invention also provides pharmaceutical compositions containing the coated CaO2 nanoparticles, together with at least one photosensitiser, sonosensitiser, or radiosensitiser and, optionally, at least one pharmaceutical carrier or excipient.

Abstract: The invention relates to microbubble complexes for use in methods of sonodynamic therapy which comprise a microbubble attached to or otherwise associated with one or more linking groups, each linking group being bound to at least one sonosensitising agent and at least one chemotherapeutic agent. It further relates to the microbubble complexes themselves and to pharmaceutical compositions which contain them. The invention is particularly suitable for the treatment of deep-sited tumors, in particular pancreatic cancer.

Abstract: The invention provides CaO2 nanoparticles having a pH-responsive coating for use in a method of adjuvant therapy of hypoxic tumour cells or tissues. The nanoparticles find particular use in enhancing cancer therapies that depend on oxygen to exert their effect, such as photodynamic therapy (PDT), sonodynamic therapy (SDT), and radiotherapy. The invention also provides pharmaceutical compositions containing the coated CaO2 nanoparticles, together with at least one photosensitiser, sonosensitiser, or radiosensitiser and, optionally, at least one pharmaceutical carrier or excipient.

Abstract: The invention relates to methods of sonodynamic therapy comprising the co-administration of a microbubble-chemotherapeutic agent complex together with a microbubble-sonosensitiser complex. It further relates to pharmaceutical compositions comprising these complexes and their use in methods of sonodynamic therapy and/or sonodynamic diagnosis. Such methods find particular use in the treatment of cancer, e.g. pancreatic cancer.

Abstract: A method and apparatus are disclosed for securing a first metallic target object to a further metallic target object. The apparatus includes a heating element for heating a bonding interface region between juxtaposed portions of a first and further metallic target object, at least one chamber body portion securable around the interface region to form a chamber region surrounding the interface region, a pump member for at least partially removing oxygen from the chamber region and a target object locating unit arranged to locate portions of the first and further target objects in a juxtaposed position.

Abstract: A method of delivering a micro-organism to an animal, the method comprising providing a formulation comprising a micro-organism suspended in or on a matrix; providing a fee stream for the animal; detaching micro-organisms from the matrix; and entraining detached micro-organisms into the feed stream. An apparatus for delivering a micro-organism to an animal is also described.

Abstract: Applicants describe a cell ablation apparatus comprising: electric field signal generating circuitry for generating an electric field signal; an electric field delivery component connected to receive the electric field signal and operable to deliver an electric field to a treatment site; ultrasound signal generating circuitry for generating an ultrasound signal; an ultrasound delivery component connected to receive the ultrasound signal and operable to deliver ultrasound to the treatment site; and a controller operable to control the electric field signal generating circuitry and the ultrasound signal generating circuitry in order to ablate a cell at the treatment site. Various electrode configurations suitable for use in such an apparatus and independently are described.

Abstract: The invention relates to a system, process and apparatus for separating biosorbent and sorbate. Biomass enclosed within a membrane system is coupled to an electrode, which is capable of being placed in contact with the sorbate containing material in the presence of a counter electrode. An electric field may be discharged across the electrodes and ionic species will migrate into the membrane enclosed system. The migrated species within the membrane can be taken up and processed by the biosorbtive processes of the biomass. The system may be used to remove dye stuffs, metal, heavy metals, radionuclides and other pollutants from natural and artificial sources.

Abstract: The invention relates to a system, process and apparatus for separating biosorbent and sorbate. Biomass enclosed within a membrane system is coupled to an electrode, which is capable of being placed in contact with the sorbate containing material in the presence of a counter electrode. An electric field may be discharged across the electrodes and ionic species will migrate into the membrane enclosed system. The migrated species within the membrane can be taken up and processed by the biosorbtive processes of the biomass. The system may be used to remove dye stuffs, metal, heavy metals, radionuclides and other pollutants from natural and artificial sources.

Abstract: An adaptive control system and method for a multi-cylinder internal combustion engine is provided wherein a perturbation generator perturbs an engine control parameter of a cylinder about a base-line value, and a measuring means measures the slope of an engine output with respect to perturbations in the engine control parameter caused by the perturbation generator. A correction unit employs the measured slope to correct at least one engine control parameter of the engine so as to obtain a desired value of the slope measured by the measuring means. The corrected control parameter can be the same or different from the perturbed control parameter. The perturbation generator operates in a first perturbation mode in an upper speed range of the engine and in a second perturbation mode in a lower speed range of the engine. The slope measuring unit operates in different measurement modes corresponding to these perturbation modes.