An Injectable Implant Providing Long-Acting Drug Delivery for the Treatment of Chronic disease
Lead Research Organisation:
University of Liverpool
Department Name: Chemistry
Abstract
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.
This proposal seeks to develop a new drug delivery system that could be easily injected into the body and would provide long-acting drug release. This technology would address issues caused by poor medication adherence. The drug delivery system would be composed of responsive polymer nanoparticles and drug nanoparticles that form a nanocomposite, entrapping a reservoir of drug upon injection into the body. After the drug has been released the materials would degrade into non-toxic components and leave the body.
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.
This proposal seeks to develop a new drug delivery system that could be easily injected into the body and would provide long-acting drug release. This technology would address issues caused by poor medication adherence. The drug delivery system would be composed of responsive polymer nanoparticles and drug nanoparticles that form a nanocomposite, entrapping a reservoir of drug upon injection into the body. After the drug has been released the materials would degrade into non-toxic components and leave the body.
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.
Planned Impact
Economy:
Long-acting drug delivery provided by a single injection would be a major step forward for the treatment of chronic disease. Relevant utilisation of this research will provide significant benefits for the pharmaceutical industry and the healthcare sector. The burden on the NHS associated with chronic disease is huge, estimated at £77bn per annum. Any technology that can assist in the treatment of patients with long-term conditions and reduce the likelihood of complications will provide a considerable opportunity for reducing NHS costs. Additionally, such savings provide a clear opportunity for the private commercialisation of the technology. Furthermore, re-purposing existing drugs would save companies huge resources normally required to bring a new drug to market. Upon the successful completion of the proposed research, the technology could be applied to other poorly-soluble drugs and could also lead to improved sustained drug delivery for a vast range of other diseases, allowing considerable impact across therapeutic healthcare. These economic opportunities will be realised by protecting and exploiting any new intellectual property and building on the applicants' strong track record of previous successful industry collaborations. New start-up companies would attract significant investment to commercialise this technology, creating new jobs and contributing to local wealth creation. For the NHS and other healthcare providers, drug delivery via an injectable, degradable nanocomposite could lead to significant time and cost savings through the reduction in the number of invasive treatments and associated hospital visits.
Society:
An injectable, degradable nanocomposite providing long-acting drug delivery would change clinical practice, it would reduce the burden to the NHS and provide a patient requested alternative to oral administration. In this proposal we aim to develop the technology to deliver drugs to treat five indications; epilepsy, HIV, cardiovascular disease, transplant rejection and diseases of the back of the eye. These diseases effect over 8 million people in the UK. Currently, poor adherence results in patients with increase numbers of complications meaning increased lost work days and the need for greater community support. Ultimately, poor adherence in reduces a patient's healthy lifespan. A long-acting implant would potentially dramatically improve quality of life for patients requiring chronic dosing overcoming poor adherence.
The PDRAs employed on the proposed project will develop a broad range of specialised skills in the fields of polymer chemistry, colloid science, materials science and pharmacology. In addition, all PDRAs will expand on their experience of successfully undertaking multidisciplinary research. Given that all the PDRAs will attend at least two conferences, they will also further develop their presentation skills and obtain networking opportunities through exposure to the UK and international research communities. Working in partnership with clinical academic colleagues will also broaden their experiences of different research environments. They will also undertake outreach activities, including those with potential end-users. Therefore these researchers will be have enhanced employment opportunities at the end of their employment on the project.
Long-acting drug delivery provided by a single injection would be a major step forward for the treatment of chronic disease. Relevant utilisation of this research will provide significant benefits for the pharmaceutical industry and the healthcare sector. The burden on the NHS associated with chronic disease is huge, estimated at £77bn per annum. Any technology that can assist in the treatment of patients with long-term conditions and reduce the likelihood of complications will provide a considerable opportunity for reducing NHS costs. Additionally, such savings provide a clear opportunity for the private commercialisation of the technology. Furthermore, re-purposing existing drugs would save companies huge resources normally required to bring a new drug to market. Upon the successful completion of the proposed research, the technology could be applied to other poorly-soluble drugs and could also lead to improved sustained drug delivery for a vast range of other diseases, allowing considerable impact across therapeutic healthcare. These economic opportunities will be realised by protecting and exploiting any new intellectual property and building on the applicants' strong track record of previous successful industry collaborations. New start-up companies would attract significant investment to commercialise this technology, creating new jobs and contributing to local wealth creation. For the NHS and other healthcare providers, drug delivery via an injectable, degradable nanocomposite could lead to significant time and cost savings through the reduction in the number of invasive treatments and associated hospital visits.
Society:
An injectable, degradable nanocomposite providing long-acting drug delivery would change clinical practice, it would reduce the burden to the NHS and provide a patient requested alternative to oral administration. In this proposal we aim to develop the technology to deliver drugs to treat five indications; epilepsy, HIV, cardiovascular disease, transplant rejection and diseases of the back of the eye. These diseases effect over 8 million people in the UK. Currently, poor adherence results in patients with increase numbers of complications meaning increased lost work days and the need for greater community support. Ultimately, poor adherence in reduces a patient's healthy lifespan. A long-acting implant would potentially dramatically improve quality of life for patients requiring chronic dosing overcoming poor adherence.
The PDRAs employed on the proposed project will develop a broad range of specialised skills in the fields of polymer chemistry, colloid science, materials science and pharmacology. In addition, all PDRAs will expand on their experience of successfully undertaking multidisciplinary research. Given that all the PDRAs will attend at least two conferences, they will also further develop their presentation skills and obtain networking opportunities through exposure to the UK and international research communities. Working in partnership with clinical academic colleagues will also broaden their experiences of different research environments. They will also undertake outreach activities, including those with potential end-users. Therefore these researchers will be have enhanced employment opportunities at the end of their employment on the project.
Publications
Arshad U
(2020)
Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics.
in Clinical pharmacology and therapeutics
Assmus F
(2022)
Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19
in Microorganisms
Boffito M
(2021)
Toward Consensus on Correct Interpretation of Protein Binding in Plasma and Other Biological Matrices for COVID-19 Therapeutic Development.
in Clinical pharmacology and therapeutics
Box HJ
(2024)
Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters.
in The Journal of antimicrobial chemotherapy
Elbaz N
(2023)
Layer by layer self-assembly for coating a nanosuspension to modify drug release and stability for oral delivery
in Food Hydrocolloids
Elbaz N
(2021)
Redispersible nanosuspensions as a plausible oral delivery system for curcumin
in Food Hydrocolloids
Flexner C
(2022)
The LEAP Process: Streamlining the Development of Long-Acting Products and Formulations for Infectious Diseases.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Gallardo-Toledo E
(2023)
Chemoprophylactic Assessment of Combined Intranasal SARS-CoV-2 Polymerase and Exonuclease Inhibition in Syrian Golden Hamsters
in Viruses
Gray DM
(2022)
Dual-responsive degradable core-shell nanogels with tuneable aggregation behaviour.
in RSC advances
Hiscox JA
(2021)
Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance?
in The Journal of antimicrobial chemotherapy
Hogarth C
(2024)
Navigating the challenges of lipid nanoparticle formulation: the role of unpegylated lipid surfactants in enhancing drug loading and stability
in Nanoscale Advances
Hogarth C
(2021)
Evaluating the impact of systematic hydrophobic modification of model drugs on the control, stability and loading of lipid-based nanoparticles.
in Journal of materials chemistry. B
Johnson L
(2021)
Multi-stimuli-responsive aggregation of nanoparticles driven by the manipulation of colloidal stability.
in Nanoscale
Kinvig H
(2023)
Physiologically Based Pharmacokinetic Modelling of Cabotegravir Microarray Patches in Rats and Humans
in Pharmaceutics
Neary M
(2022)
A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Neary M
(2023)
Quantitation of tizoxanide in multiple matrices to support cell culture, animal and human research
in Journal of Chromatography B
Niezabitowska E
(2023)
Understanding the Degradation of Core-Shell Nanogels Using Asymmetrical Flow Field Flow Fractionation.
in Journal of functional biomaterials
Niezabitowska E
(2020)
Insights into the internal structures of nanogels using a versatile asymmetric-flow field-flow fractionation method.
in Nanoscale advances
Pertinez H
(2021)
Pharmacokinetic modelling to estimate intracellular favipiravir ribofuranosyl-5'-triphosphate exposure to support posology for SARS-CoV-2.
in The Journal of antimicrobial chemotherapy
Rajoli RKR
(2021)
Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis.
in British journal of clinical pharmacology
Sirijatuphat R
(2022)
Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study
in Emerging Microbes & Infections
Taylor JM
(2020)
Using pyrene to probe the effects of poloxamer stabilisers on internal lipid microenvironments in solid lipid nanoparticles.
in Nanoscale advances
Thomas D
(2022)
Prospects for Long-Acting Treatments for Hepatitis C
in Clinical Infectious Diseases
Town A
(2019)
Understanding the Phase and Morphological Behavior of Dispersions of Synergistic Dual-Stimuli-Responsive Poly(N-isopropylacrylamide) Nanogels.
in The journal of physical chemistry. B
Town AR
(2019)
Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size.
in Journal of materials chemistry. B
Walker LE
(2022)
An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.
in Clinical pharmacology and therapeutics
Description | We have developed a new type of degradable in situ forming implant that has the potential to provide long-acting drug delivery. Our new materials offer the potential to be injected and form an implant in the body that can slowly release drugs over a long time period. This would remove the need for patients to take daily tablets used in the treatment of chronic diseases. |
Exploitation Route | This work has demonstrated the potential of the degradable in situ forming implant technology we have developed. Thus providing a new tool for researchers and scientists who are developing long-acting drug delivery systems. We also plan to progress this work to the next stage of pre-clinical trials. |
Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
Description | Active mapping of biological substrates for crop care and personal care applications |
Amount | £39,674 (GBP) |
Funding ID | EP/R511729/1 |
Organisation | University of Liverpool |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2022 |
Description | Presented at Chemistry Webinar, Department of Chemistry, University of Education, Attock Campus, Pakistan, February 2023 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Tom McDonald presented a talk titled "Designing dual responsive nanogels as an in situ forming drug delivery system" |
Year(s) Of Engagement Activity | 2023 |