An Injectable Implant Providing Long-Acting Drug Delivery for the Treatment of Chronic Disease

Project overview

Within Europe, chronic diseases are currently the leading cause of mortality and morbidity. In England alone, there are 15m people with long-term conditions who are estimated to account for 70% of the total health and social care spend. A significant factor in the management of chronic disease is the long-term nature of the treatment.

Although often very efficient, therapies are only effective when combined with long-term medication adherence from the patient. Unfortunately, patient adherence is typically poor within long-term disease patient populations; only about 50% of patients adhere to their treatment regimes. Poor adherence can be addressed by the simplification of therapeutic regimes through reducing the dosing frequency. For example, when self-administered treatment regimens such as oral dosing are replaced with long acting formulations adherence can be greatly improved. Additionally, reducing the frequently of dosing is known to be appealing to patients with long-term therapy requirements.

In order to accelerate the development of this novel technology toward clinical use, this project will consist of closely integrated materials synthesis and biological assessment. The materials involved will be simultaneously prepared and evaluated in the presence of cells to check that they are biologically compatible. The responsive polymer nanoparticles will be synthesised to combine responsive behaviour with tuneable degradation, while the design of the drug nanoparticles will allow the drug release rate to be altered. A small number of optimised materials will undergo detailed biological evaluation. The resulting novel, biodegradable, nanocomposite material would have appropriate physical and biological properties for injection into the body. This technology will provide tuneable, long-acting release of drugs for the treatment of chronic disease.

Objectives

• Synthesise and characterise degradable, synergistic dual-stimuli responsive nanogels.
• Synthesise and characterise solid drug nanoparticles (SDNs) for the treatment of chronic diseases.
• Establish synergistic dual-stimuli responsive gelation of cytocompatible, high drug loading nanogel/SDN nanocomposites.
• Evaluate the drug release behaviour of the nanogel/SDN nanocomposites in vitro and in vivo.

Awarding body

Related publications

Understanding the Phase and Morphological Behavior of Dispersions of Synergistic Dual-Stimuli-Responsive Poly(N‑isopropylacrylamide) Nanogels 

Adam Town, Edyta Niezabitowska, Janine Kavanagh, Michael Barrow, Victoria R. Kearns, Esther García-Tuñon, and Tom O. McDonald

Insights into the internal structures of nanogels using a versatile asymmetric-flow field-flow fractionation method 
Edyta Niezabitowska, Adam R. Town, Bassem Sabagh, Marissa D. Morales Moctezuma, Victoria R. Kearns, Sebastian G. Spain, Steve P. Rannard and Tom O. McDonald 

Dual-responsive degradable core–shell nanogels with tuneable aggregation behaviour
Dominic Gray, Adam Town, Edyta Niezabitowska, Steve Rannard, and  Tom O. McDonald

Multi-stimuli-responsive aggregation of nanoparticles driven by the manipulation of colloidal stability
Luke Johnson, Dominic Gray, Edyta Niezabitowska and Tom O. McDonald

Using pyrene to probe the effects of poloxamer stabilisers on internal lipid microenvironments in solid lipid nanoparticles
Jessica Taylor, Kyle Scale, Sarah Arrowsmith, Andy Sharp, Sean Flynn, Seve Rannard and Tom O. McDonald

Evaluating the impact of systematic hydrophobic modification of model drugs on the control, stability and loading of lipid-based nanoparticles
Cameron Hogarth, Keith Arnold, Andrew McLauchlin, Steve Rannard, Marco Siccardi and Tom O. McDonald 

Redispersible nanosuspensions as a plausible oral delivery system for curcuminNancy Elbaz, Lee Tatham, Andrew Owen, Steve Rannard and Tom O.McDonald

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