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  • Drug Design, Analysis and Delivery

    Pharmacy Lab

Research in the group aims to design and analyse new drugs, and to develop new nanocarrier-based medicines (nanomedicines) for the delivery and targeting of therapeutic agents in the treatment of inflammatory diseases, cancers, infections, asthma and diabetes.

This research group contributes to the cross-disciplinary research sub-theme: Evidence from Bench to Bedside.

EXPERTISE AND SUBJECT AREAS

We are currently developing vaccine formulations for intranasal spray administration. This is taking place using proliposome approach to formulation of liposomes that would entrap a model protein vaccine. Other nanotechnologies such as these based on surfactants and polymers are also considered using a wide range of formulations such as spray drying and freeze drying. Liposomes, niosomes and microemulsions are also applicable in the pulmonary delivery of antiasthama and antifungal drugs using novel inhalation devices such as vibrating mesh nebulisers. The influence of formulation variables on drug delivery to the deep lung using a model in vitro system and laser diffraction is evaluated. We are equipped with state of the art facilities to perform high quality studies in this area.

A novel research area focuses on surface engineered dendrimers which are designed to enhance drug transport via the gastrointestinal tract and blood-brain barrier. Dendrimer-based carriers have been designed so that they are capable of enhancing solubility, bypassing efflux transporter systems and crossing biological barriers. Ongoing research is exploring the targeting of the central nervous system by engineering dendrimers that are capable of penetrating the blood brain barrier. This might comprise a future strategy for the treatment of neurodegenerative diseases and brain tumours such as glioma.

Novel hydrogels and biodegradable polymers are being developed for use in drug delivery, biomedical devices and tissue engineering. For instance, targetable polymeric nanocarriers are investigated for the selective delivery of small organic molecules and macromoleucles such as genes and proteins for the treatment of various diseases including cancer and inflammatory conditions (e.g. rheumatoid arthritis). The biological fate and in vivo activity of these nanosystems are being studied using techniques such as FACS, confocal imaging and other molecular biology tools.

Due to the versatility of polymeric drug delivery systems, their ability to enhance permeation of chemicals through the skin is also being studied using a simple Franz diffusion cell model.
Other expertise within the group includes the chemical synthesis and biological evaluation of compounds with potential anticancer and antibacterial properties and the development of new synthetic methods to make such compounds.

We are also interested in exploiting molecular conformation in the design and preparation of diagnostic probes to detect enzymes over-expressed in disease and the biomembrane interaction of novel nanosized drug delivery systems.

Additional expertise includes computer-aided drug design. This is being applied in the search for novel dopamine selective ligands, phosphodiesterase inhibitors and retinoic acid derivatives. Compounds identified are synthesised and subsequently screened for pharmacological activity.

A study of novel cellulose hydrogels for possible application in controlled drug release and wound healing dressings is also being undertaken.

Impact

We publish high quality research in peer-reviewed international academic journals and a number of patents have resulted from work in the group. Members of the group have worked are recognised as international leaders in their field and collaborate with groups across the world.

  • Joint funding received from the Sydney Driscoll Neuroscience Foundation and Brain Tumour North West to support a PhD studentship exploring the development of novel compounds for the treatment of glioma.

Publications and outputs

Teow, H. M., Zhou, Z., Najlah, M., Yusof, S. R., Abbott, N. J. D’Emanuele, A.
Delivery of Paclitaxel Across Cellular Barriers Using a Dendrimer-based Nanocarrier
International Journal of Pharmaceutics, 441, 701-711, 2013.

Synthetic oligoureas of metaphenylenediamine mimic host defence peptides in their antimicrobial behaviour: Sarah R. Dennison, David A. Phoenix, and Timothy J. Snape,* Bioorg. Med. Chem. Lett., 2013, In Press

Preparation of benzamidobenzoic acid derivatives and analogs for use as retinoic acid receptor α agonists.
Corcoran, Jonathan Patrick Thomas; Kalindjian, Sarkis Barret; Borthwick, Alan David; Adams, David Reginald; Brown, Jane Theresa; Taddei, David Michel Adrien; Shiers, Jason John; PCT Int. Appl. (2011), WO 2011027106 A1 20110310.

Elhissi A, Hidayat K, Phoenix DA, Mwesigwa E, Crean S, Ahmed W, Faheem A, Taylor KM. Air-jet and vibrating-mesh nebulization of niosomes generated using a particulate-based proniosome technology. International Journal of Pharmaceutics, 444, 193-199, 2013.

Elhissi A, Jama F, Ahmed W, Taylor K. Method of Producing nebuliser composition. Pub. No. WO/2013/005020, International Application No. PCT/GB2012/051543, Publication Date: 10.01.2013, International Filing Date: 02.07.2012.

Related Projects

Developing novel asymmetric reactions for the synthesis of pharmaceutically relevant compounds

Exploiting activated esters in novel chemoselective amide-forming reactions

Design, synthesis and biological evaluation of novel heteroaromatic compounds for the potential treatment of glioma

Design, synthesis and biophysical analysis of novel foldamers to overcome resistant strains of bacterial infection

Targeted nanoparticulate drug delivery system for anti-cancer therapy

Nanoparticle design for the treatment of glioblastoma

Nanoparticulate drug delivery system for enhanced skin permeation

A Study of silanised derivatives of cellulose and starch for their absorbent and swelling properties.

A combined dopamine D1 agonist/D2 antagonist for the treatment of schizophrenia.

Application of combined virtual screening/synthetic feasibility in the search for novel ligands with potential pharmacological activity.

Use of dendrimer carriers to overcome cellular barriers.