Project overview
Within Europe, chronic diseases are currently the leading cause of mortality and morbidity. In England alone, there are 15 million 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.
Findings
- The incorporation of the solid drug nanoparticle into the nanogel tuned the in vitro (outside of a body lab study) release of rapamycin; the percentage of rapamycin released after 48 hours was higher in the solid drug nanoparticle formulation in comparison to the nanogel/sold drug nanoparticle nanocomposites evaluated
- Rapamycin is detected in plasma up to 14 days after single subcutaneous administration of nanogel/solid drug nanoparticle nanocomposite
- In vitro - in vivo correlation analysis showed correlation in the shape of the release profile but not in magnitude. Parameters present in vivo but not in vitro, such as biological processes, might explain the differences in magnitude observed in vitro and in vivo.
Implications
This means this new drug delivery system could reduce oral drug regimens for patients. Drugs using this new system could only need administering every two weeks, reducing patient drug burden.
Next Steps
- Develop new nanocomposites with other drugs used for the treatment of chronic diseases and evaluate their in vitro drug release and in vivo pharmacokinetic profiles
- Evaluate the impact of biological processes, such as granuloma formation (an immune response), caused by drug release
- Determine the biodegradability of the nanocomposites in vivo in order to ensure the drug is accepted by the body and performs its intended function.
Awarding body
Related publications
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
Using pyrene to probe the effects of poloxamer stabilisers on internal lipid microenvironments in solid lipid nanoparticles
Evaluating the impact of systematic hydrophobic modification of model drugs on the control, stability and loading of lipid-based nanoparticles
Redispersible nanosuspensions as a plausible oral delivery system for curcumin
Nancy Elbaz, Lee Tatham, Andrew Owen, Steve Rannard and Tom O.McDonald