Molecular strategy for developing instant nanomedicine
Lead Research Organisation:
University College London
Department Name: Surgical Biotechnology
Abstract
CONTEXT: There exists a pressing clinical need in the UK and globally to make strategy for generating therapeutics within or in close proximity to clinical facilities for timely delivery to patients, i.e., point-of-care (POC) manufacturing. This concept encompasses the production of drugs, vaccines, cell, and nucleic acid therapies (e.g., gene therapies, mRNA vaccines, nanomedicines, etc.) for the treatment of a diverse array of diseases, ranging from rare conditions to more prevalent ones such as cancer, infections, severe burns, or diabetes.
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently brought forth a new regulatory framework specifically designed for the in-hospital POC manufacturing of therapies. This initiative will alleviate the existing challenges of using therapeutics with a limited shelf-life and supply-chain issues such as low-temperature storage (e.g., mRNA nanovaccines) and will expand the range and availability of new innovative therapies in the NHS.
CHALLENGES THE PROJECT ADDRESSES: Nanomedicine despite its initial successes and effectiveness with products like Doxil®, Abraxane®, Marqibo®, Stimuvax®, etc., it has not fully realized its potential. Challenges such as manufacturing complexity, formulation intricacies, upscaling difficulties, low solubility, colloidal stability loss during storage, limited shelf-life, and stringent storage conditions (e.g., -80 °C), as encountered with COVID-19 vaccines using solid-lipid nano formulations (e.g., Pfizer/BioNTech and Moderna), are contributory factors that limit its full impact.
Therefore, a simpler manufacturing and formulation strategy together with long-term stability for storage are unmet crucial needs. We propose to develop an innovative molecular platform for a point-of-care instant nano formulation (inFORM) to address the principal bottleneck of manufacturing therapeutics on-site.
AIMS & OBJECTIVES: The focused aims of this project are to:
WP1(1-9months) Rationally design a molecular strategy to develop a self-assembled peptide for making instant drug formulation: We will develop a rationally designed peptide library for self-assembly and capable of simple and quick drug encapsulation for point-of-care (POC) manufacturing.
WP2(9-18months): Screening encapsulation efficiency for selected FDA approved drugs and nucleic acids with different chemical structure to build inFORM library: The inFORM library will be optimised for instant co-acervation, packaging and self-assembling to an easy formulation by manipulating the co-acervation and self-assembly process by simple methods such as by mixing, small change in pH, ionic strength, heat, redox potential, sonication, vortexing etc for simple and quick drug formulation.
The proposed inFORM project is perfectly aligned with this EPSRC call 'to address key bottlenecks in future medicines manufacturing pipeline'. The inFORM proposals will serve the purpose of this call 'through speculative, high-risk ideas that could potentially offer high reward'.
POTENTIAL IMPACT: The inFORM approach will address one of the principal bottleneck issues of existing nanomedicine and point-of-care instant manufacturing. A library of peptide nanoarchitectures will be developed for coacervation and instant packaging of drugs and nucleic acids. Designing and employing such coacervating peptides to serve as a specific nano formulation with the proposed strategy has never been developed and tested. Therefore, this innovative approach can generate significant step-change results for future study, IPs, and can have significant impacts on future steps in nanomedicine and point-of care therapy both clinically and commercially. The success of inFORM will have a significant impact on modular manufacture (e.g., hospital, GP, OPD, pharmacies), mobile manufacture, POC manufacture and potentially home-based manufacture to fulfil the UK mission.
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has recently brought forth a new regulatory framework specifically designed for the in-hospital POC manufacturing of therapies. This initiative will alleviate the existing challenges of using therapeutics with a limited shelf-life and supply-chain issues such as low-temperature storage (e.g., mRNA nanovaccines) and will expand the range and availability of new innovative therapies in the NHS.
CHALLENGES THE PROJECT ADDRESSES: Nanomedicine despite its initial successes and effectiveness with products like Doxil®, Abraxane®, Marqibo®, Stimuvax®, etc., it has not fully realized its potential. Challenges such as manufacturing complexity, formulation intricacies, upscaling difficulties, low solubility, colloidal stability loss during storage, limited shelf-life, and stringent storage conditions (e.g., -80 °C), as encountered with COVID-19 vaccines using solid-lipid nano formulations (e.g., Pfizer/BioNTech and Moderna), are contributory factors that limit its full impact.
Therefore, a simpler manufacturing and formulation strategy together with long-term stability for storage are unmet crucial needs. We propose to develop an innovative molecular platform for a point-of-care instant nano formulation (inFORM) to address the principal bottleneck of manufacturing therapeutics on-site.
AIMS & OBJECTIVES: The focused aims of this project are to:
WP1(1-9months) Rationally design a molecular strategy to develop a self-assembled peptide for making instant drug formulation: We will develop a rationally designed peptide library for self-assembly and capable of simple and quick drug encapsulation for point-of-care (POC) manufacturing.
WP2(9-18months): Screening encapsulation efficiency for selected FDA approved drugs and nucleic acids with different chemical structure to build inFORM library: The inFORM library will be optimised for instant co-acervation, packaging and self-assembling to an easy formulation by manipulating the co-acervation and self-assembly process by simple methods such as by mixing, small change in pH, ionic strength, heat, redox potential, sonication, vortexing etc for simple and quick drug formulation.
The proposed inFORM project is perfectly aligned with this EPSRC call 'to address key bottlenecks in future medicines manufacturing pipeline'. The inFORM proposals will serve the purpose of this call 'through speculative, high-risk ideas that could potentially offer high reward'.
POTENTIAL IMPACT: The inFORM approach will address one of the principal bottleneck issues of existing nanomedicine and point-of-care instant manufacturing. A library of peptide nanoarchitectures will be developed for coacervation and instant packaging of drugs and nucleic acids. Designing and employing such coacervating peptides to serve as a specific nano formulation with the proposed strategy has never been developed and tested. Therefore, this innovative approach can generate significant step-change results for future study, IPs, and can have significant impacts on future steps in nanomedicine and point-of care therapy both clinically and commercially. The success of inFORM will have a significant impact on modular manufacture (e.g., hospital, GP, OPD, pharmacies), mobile manufacture, POC manufacture and potentially home-based manufacture to fulfil the UK mission.
