Non invasive methods to accelerate the development of injectable therapeutic depots

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Our vision is to create a low-cost, non-invasive depot monitoring tool that can provide key information about the state of an injected depot in real time. This low-cost device will have applications in preclinical studies and in the clinical setting for long-acting depot development to accelerate the process. We envisage that the device could be developed to benefit patients, including different skin tones, at home as a way of assessing and monitoring depot performance, enabling personalisation of the depot dose and the administration schedule in the future.Our project addresses, and is timely in the context of, the current rapid increase in interest in therapeutic drug depots within the pharmaceutical industry as medicines capable of achieving long term delivery of classical small-molecule drugs and biologics for the treatment of diseases including, cancer, HIV, neurological disease and psychoses. A long-acting depot aims to control patient therapy over a period of weeks or months; it eliminates the necessity for repeated daily injections addressing issues such as variation in plasma and tissue drug levels or non-compliance in long term patient therapy. Demand is further driven by the increased proportion of drugs in development requiring long-acting injectable technologies, particularly biologicals. Currently, introduction to the market of a long-acting injectable depot of any drug takes ~10 years of development after approval of its oral formulation. This is due to the requirement to understand the depot's behaviour within the injection site tissue, and linked effects on release, and bioavailability of the drug for therapy. Consequently, it is extremely difficult to develop long-acting depots with a guaranteed specific release profile in-vivo for individual patients. Moreover, there is no method for real-time monitoring of their performance in preclinical studies during medicine development or during patient therapy.Our goal is to develop the concept of a low-cost, non-invasive injectable depot characterisation tool based on photoacoustic principles that can provide information on depot characteristics and in-vivo local tissue response.Objectives are:To define the specification and build prototype photoacoustic instrumentation that would form the basis of a low-cost device capable of measuring key parameters of the depot's behaviourDesign, fabrication and optimisation of a long-acting depot formulation required for data acquisition by the prototype photoacoustic instrumentation. This will include selection of depot constituent components and a drug, as well as a selection of appropriate photoacoustic contrast agents.Acquisition of photoacoustic signal in 'model' biological conditions using (i) established in-vitro tissue-mimicking phantoms and (ii) in preclinical, in-vivo injection into subcutaneous rat tissue.To model photoacoustic signals from the depot using in-house and widely available codeMonitoring key parameters of injected depot in real-time will provide surveillance information required to understand the depot's behaviour and aid in prediction of drug release and its bioavailability. We propose the use of photoacoustic monitoring and measurement to gather this information in a safe, non-invasive manner initially preclinically and subsequently envisage its use in clinical trials and therapy. This is a novel and pragmatic approach to the problem with a strong pathway to a low-cost implementation.