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Sustainable and controlled drug delivery to fight global antimicrobial resistance (AMR) using hybrid porous nano containers


   Faculty of Life Sciences


About the Project

Growing antimicrobial resistance (AMR) is one of the major global challenges and it is often linked to the use of unnecessarily high doses of orally administered antibiotics following medical surgeries and infections. With a rise in life expectancy globally the demand for such medical intervention increases, and so does the associated use of antibiotics, increasing the risks of AMR (1). Reducing the use of antibiotics and the need for revision surgery is a long term challenge, so optimal dosing, duration of therapy and developing alternatives to antibiotics can also be considered as strategies to reduce AMR. In this project we will develop a class of biodegradable hybrid material that can be used to manufacture suture materials and other medical devices, such as patches which can simultaneously store and deliver antibiotics to specific targeted sites (2-5). Upon successful development these materials can be also used for delivering anti-inflammatories and nitric oxide in a slow and controlled rate to specific targeted sites (2-5).

Metal-organic frameworks (MOFs) are a versatile class porous materials, developed recently, with very high accessible surface area (6). The functional groups inside the pores of the MOFs can be modified to interact and store different drug molecules, and this class of materials has shown promising results for drug delivery applications (7). However, the majority of the MOFs suffer from poor stability. This project will take advantage of this drawback, so that the MOFs will decompose with time together with biodegradable polylactic acid (PLA) and polycaprolactone (PCL) polymer matrices thus delivering guest drug molecules to targeted sites.

The size of the MOF particles play an important role in delivering the drugs and part of this project will investigate the optimization of the MOF particles for effective penetration of cell walls for delivering the drug across cell membranes.

Both MOFs and PLA/PCL are of interest for drug delivery applications and are the subject of significant levels of research. However, the combination of these two classes of materials offers exciting potential for bioresorbable drug carriers which can be integrated into novel biomedical devices such as implants. This project will explore this highly promising area to develop novel composite materials which can be used to manufacture devices that can deliver antimicrobial drugs locally, without exposing the rest of the body to the drugs unnecessarily. This will reduce the usage of strong non-targeted antibiotics in excess, and therefore, help to reduce the growing problem of AMR which is a global problem recognised by World Health Organization (8).

Aims and objectives

The project will focus on identifying appropriate MOFs that can host a number of drugs that are used to treat external and internal bacterial infections. The selected MOFs will be synthesized in the first six months of the project. This part will follow loading of the MOFs using antimicrobial drugs, and in parallel optimization of size of the MOF particles in nanometer range using continuous flow technique (in collaboration with Edinburgh). The student will receive training on required techniques (synthis, and equipment: X-ray diffraction, spectroscopic techniques, HPLC, UV-Vis, Thermal analysis, electron microscopy). The characterization of the MOFs and drug loading will generate significant amount of data at this phase.

In the following phase, research will focus more on optimization of MOF-size, drug loading, and synthesis of polymer composites.

In the next and final part of the project the focus will be more on drug delivery/release studies, and optimization of polymer-MOF composites. The composites will be then used to develop pathches and threads using compress molding and extrusion techniques, and their drug release properties will be studied for potential medical applications.

How to apply

Applications can be made via the University of Bradford web site.


References

(1) Cao, J.; Song, W.; Gu, B.; Mei, Y. N.; Tang, J. P.; Meng, L.; Yang, C. Q.; Wang, H. J.; Zhou, H. Correlation Between Carbapenem Consumption and Antimicrobial Resistance Rates of Acinetobacter baumannii in a University-Affiliated Hospital in China. J. Clin. Pharmacol. 2013, 53, 96-102.
(2) Fleming, G.; Aveyard, J.; Fothergill, J. L.; McBride, F.; Raval, R.; D'Sa, R. A. Nitric Oxide Releasing Polymeric Coatings for the Prevention of Biofilm Formation. Polymers 2017, 9, 17.
(3) De Brabander, C.; Vervaet, C.; Remon, J. P. Development and evaluation of sustained release mini-matrices prepared via hot melt extrusion. J. Control. Release 2003, 89, 235-247.
(4) Qiu, Y.; Park, K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev. 2012, 64, 49-60.
(5) Haikal, R. R.; Hua, C.; Perry, J. J.; O'Nolan, D.; Syed, I.; Kumar, A.; Chester, A. H.; Zaworotko, M. J.; Yacoub, M. H.; Alkordi, M. H. Controlling the Uptake and Regulating the Release of Nitric Oxide in Microporous Solids. ACS Appl. Mater. Interfaces 2017, 9, 43520-43528.
(6) Furukawa, H.; Cordova, K. E.; O'Keeffe, M.; Yaghi, O. M. The Chemistry and Applications of Metal-Organic Frameworks. Science 2013, 341, 1230444-12304412.
(7) Huxford, R. C.; Della Rocca, J.; Lin, W. B. Metal-organic frameworks as potential drug carriers. Curr. Opin. Chem. Biol. 2010, 14, 262-268.
(8) Prestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015; 109, 309-18.

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