John Tsibouklis Lab
Our current laboratory research
Polymeric implant materials with pro-angiogenic properties
Despite significant improvements in the performance of drug-eluting stents, the current impetus for the considerable research activities towards targeted drug delivery to atherosclerotic plaques is provided by the continuous need to reduce the incidence of implantation-associated thrombosis and also by the need to decrease the complexity of such devices. Since stent-induced thrombosis has been linked to local inflammation and poor vascularisation, much research has focused on the combined use of anti-inflammatory drugs and biomaterials that promote angiogenesis. Utilising the combined therapeutic effects of aspirin (prevents thrombosis formation by inhibiting the production of thromboxane), dipyridamole (prevents endogenous adenosine action by blocking its cellular uptake and thus increasing its extracellular concentration, leading to increase in vasodilation) and lactic acid (causes vasodilatation and increased blood flow) this project aims to develop and evaluate an aspirin-terminated, dipyridamole-cored, star-shaped polylactic acid molecular construct as a bio material that may offer the combined benefits of induced angiogenesis and inflammation prevention.
The work is conducted in collaboration with Drs Nagarajan, Kiran and Reddy, Industrial Chemistry and Biomaterials Laboratories, Central Leather Research Institute, India.
Polymerisable room temperature ionic liquids (RTILs) for applications in drug delivery
The pharmaceutical industry is actively seeking drug delivery platforms that improve the therapeutic profile of existing hydrophobic drugs. Conventional carriers for the delivery of hydrophobic drugs are associated with several disadvantages: emulsions, micelles and liposomes are thermodynamically unstable; lipophilic carriers cluster in blood flow and are rapidly opsonized and massively cleared by the liver and spleen; and the loading capacity of hydrophobic drugs into hydrophilic carriers is limited. RTILs-based co-polymeric nanogels with superabsorbency for both water and organic liquids possess all the prerequisite features to address these issues: small size imparts metastability; 1-vinylimidazole and amino acid constitutional repeat units render RTILs biocompatible; good solubility of most hydrophobic drugs in organic liquids coupled with the capability of RTILs to act as superabsorbent host matrices in the same media effects significant drug loading capacity; and, superabsorbency in aqueous media allows the creation of a surface-charged drug-polymer conjugate that is capable of acting as a sustained drug delivery system. This work aims to generate an efficient method for the delivery of actives that would otherwise not be accessible to the patient.
This work also involves Professor Xinming Li, Zhongkai University of Agriculture and Engineering, China.
Mucoadhesive hydrogels for the management of xerostomia
In addition to the persistent feeling of dry mouth, people who suffer from xerostomia are very susceptible to bacterial, fungal and other transmittable mouth infections. Irrespective of the underlying reasons for the condition, the susceptibility of these people to tooth demineralisation, dental plaque and oral infections is because of their low levels of saliva. The reason for the protective function of saliva is that it presents a hydrated surface to the liquid phase, such that the attachment of microbial colonisers would involve the displacement of water associated with the macromolecular components of saliva. Consequently, the development of a saliva substitute that, unlike existing products, is retained in the oral cavity over prolonged periods of time may offer many benefits to xerostomia sufferers. To this end, and set within the context of oral care in general, this project considers the requirements for the design of hydrogel formulations with an affinity for buccal cells and aims to develop methods for evaluating the performance of these formulations as treatments for the management of xerostomia.
The ideas for this work are explored in collaboration with Jonathan Pratten (GlaxoSmithKline, UK).
New materials for the neutron capture therapy of cancer
Boron neutron capture therapy (BNCT) is a two-step approach that involves the selective delivery of 10B-rich agents to tumours, followed by irradiation with low-energy neutrons. The excited 11B nuclei that are formed undergo fission to yield high linear energy transfer (LET) particles (essentially highly cytotoxic 4He2+ and 7Li3+ ions, which move over short distances – 5 µm and 9 µm respectively - within malignant tissues), causing cell death; because of the short distances involved, the destructive radiation is confined to the cell in which the capture reaction occurs. To date, the main limitation in the clinical application of BNCT has been the synthesis of low-toxicity 10B-containing compounds that can target specific tissue at the concentration level necessary to meet the therapeutic objective – this project aims to bridge that gap.
The work involves collaborations with Drs Smith and Barbu (University of Portsmouth), Dr Calabrese (University of Kingston) and Theodoropoulos, Rova, Vizirianakis and Fatouros (Aristotle University of Thessaloniki, Greece).
Contact our researchers
View our other laboratories in the Bio-materials and Drug Delivery Research Group (BADD):