Drug Delivery
The Drug Delivery Group comprises Dr Ben Forbes, Professor Gino Martini, Dr Khuloud Al-Jamal, Dr David Begley, Dr Ken Bruce, Dr Lea Ann Dailey, Dr Jane Preston, Dr Paul Royall, Dr Stuart Jones, Dr Sarah Thomas and Emeritus Professor Gary Martin. The Group undertakes research and development in pharmaceutical technology and applies scientific principles both in the formulation of medicines and in the development and use of predictive models of drug absorption. This involves not only some of the more challenging conventional drug molecules but also the products of biotechnology. The ability of a formulation to influence the site and duration of drug action and affect therapeutic success is the major theme and results in a multifaceted research programme.
A major focus of the group is respiratory delivery and provides an excellent example of the collaborative nature of the group’s research in that all members have expertise that contributes to inhaled drug delivery research. This expertise is combined to develop novel strategies for drug delivery by inhalation and the treatment of respiratory disease. Projects extend from the science of aerosol formulations from dry powder and pressurised inhaler devices to the biopharmaceutics of particle-cell interaction, including gene therapy, and the characterisation of bacteria in lung diseases such as cystic fibrosis.
Topical delivery is another area of strength and the group has state-of-the-art facilities to design, formulate and evaluate topical preparations. These are screened in vitro using human skin diffusion models and in vivo using healthy volunteers. A number of novel devices, formulations and analytical techniques have been developed within the group and are being evaluated for commercial potential. Research into oral delivery falls into two main categories: (i) the interaction between gastrointestinal factors with lipid formulations in the intestine, and (ii) novel formulations for the delivery of drugs to the colon.
The manufacture, characterisation and evalution of nanomedicines for both drug delivery and diagnostic purposes is a third major research theme within the Drug Delivery Group. Projects range from the evaluation of carbon nanotubes as drug carriers and imaging agents and the investigation of new polymeric materials for nanomedicine development through to the evaluation of nanomedicine safety and efficacy. Nanomedicine research within the Drug Delivery Group is highly interdisciplinary where strong collaborations both with other research divisions within King’s College London are vital, as well as numerous national and international partnerships.
A fourth are of research centres on understanding the physiology and pathophysiology of barrier layers which limit and regulate molecular exchange at the interfaces between the blood and the neural tissue or its fluid spaces. Quantification and characterisation of brain and CSF delivery of drugs in health and disease forms a significant part of the studies that are undertaken. Understanding of compound delivery includes study of the generation and flow of brain interstitial fluid, in-vivo transport kinetics of a library of compounds to formulate predictive rules for brain entry, chemical modification of iron chelators to improve CNS delivery, distribution characterisation of all licensed HIV reverse transcriptase inhibitors and major HIV protease inhibitors to systematically identify single and combined drug optimisation. CNS delivery strategies employing vectors such as liposomes, nanoparticles and specific protein (amino acid) sequences are also an interest. Pathophysiological models include barrier breakdown and modulation in multiple sclerosis, barrier changes and neuropathy seen in lysosomal storage diseases, brain entry of drugs to treat African trypanosomiasis, the effects of antidepressants on glucocorticoid entry to brain, and age-related studies on CSF turnover and proteomics identification of biomarkers relevant to late life neurodegeneration.
Research is focused on the development and biopharmaceutical application of respiratory and intestinal epithelial cell culture models. Drug permeability, metabolism and gene delivery are studied:
Research is focused on the development and biopharmaceutical application of respiratory and intestinal epithelial cell culture models. Drug permeability, metabolism and gene delivery are studied: enhancement of drug transport presystemic drug metabolism epithelial pathology / toxicity
Inhaled Drug Delivery
"Inhalation biopharmaceutics" encompasses anything that may affect the rate or extent of drug absorption from the lung. Research projects in this emerging field include:
Dissolution in lung fluid Mucociliary and macrophage interactions Drug metabolism Epithelial permeability Toxicity of delivery vehicles (excipients, nanoparticles)
All these events occur at (or in) the respiratory epithelium.
Oral Drug Delivery
Current projects investigate interactions between intestinal fluid, the intestinal epithelium, orally administered drugs and formulation excipients.
Clinical Pharmaceutics
Projects with innovation aimed at improving practice in the manufacturing of pharmaceutical products.
Much of the research within the Drug Delivery group is focused on the analysis of human-associated microbes. The aim of this work is to better characterise these microbes in both health and disease.
The human lung and gut have been areas of particular importance. Most of work to date has focused on infections of the lungs of cystic fibrosis (CF) patients. It is particularly important to understand these infections given the mortality associated with respiratory failure within this patient group. Work to date has shown that a wide range of bacterial species are present and active in the CF lung. Moreover, many species that require anaerobic conditions for growth have been detected amongst a range of bacterial species not previously associated with the CF lung.
These studies are continuing – looking now at, amongst other aspects, the function of these bacteria in lung disease. Other respiratory conditions are also important. The Drug Delivery group also study the bacteria that are associated with the human gut mucosa in health and disease. These studies have shown that the bacteria associated with the gut mucosa of healthy individuals are quite distinct between individuals, yet are similar along the tract within an individual. This work is extending to study the gut in disease such as Crohn's disease and ulcerative colitis.
The Drug Delivery group work extends beyond these areas. Group members are also working on models of community development, interactions between microbe and human cells, improving and assessing therapies and their delivery. Other group members are studying the interface between environments and humans. This focuses on issues of spatial scale and incorporates aspects of stress e.g. pollutants and other chemical agents on populations and communities. This work needs the involvement of other scientists and clinicians. The Drug Delivery group is very fortunate to have the active support of such groups in the UK (currently mainly Southampton, London, Belfast and Liverpool) and abroad (USA and Australia).
The focus is to move from characterisation of what microbes are present, to develop a better understanding of the function of these microbes. From this improved understanding, similar improvements may follow in the longer term in terms of the treatment of infection.
Dr Al-Jamal has developed an extensive experience in designing and developing novel nanoscale delivery systems including dendrimers, liposomes, quantum Dots (QDs), viral vectors and chemically functionalised carbon nanotubes. Her current work involves pre-clinical translation of novel nanomaterials designed specifically for drug, siRNA, plasmid and radionuclide delivery for therapeutic or diagnostic applications. She reported for the first time the intrinsic anti-angiogenic activity of cationic poly-L-lysine dendrimers, and pioneered surface engineering of carbon nanotube-based vectors to deliver siRNA materials to the central nervous system (CNS) and solid tumours in vivo.
Current research interests:
Synthesis and characterisation of novel nanomaterials
Nanomedicine
Theranostic applications
Pharmacokinetic studies
Live small animal imaging by SPECT/CT and MRI imaging
RNAi
Gene delivery
Magnetic drug targeting
Stem cell research
Drug delivery to the BBB
Multicellular tumour spheroid cultures
Solid and metastatic tumour models.
- Development and characterisation of a new class of nitric oxide donor molecules
- S-nitrosothiol biology and metabolism
- Evaluation of the role of S-nitrosoglutathione reductase activity in asthma and other diseases
- Assessment of nanotoxicology of inhaled drug delivery vehicles and the use of nanotechnology in diagnostics
Professor Martini's research interests include the use of ultrasonic processing technology to fabricate medical devices and pharmaceutical dosage forms, the design of dosage form concepts for delivering personalised medicines and developing drug delivery systems. Professor Martini has interests in developing closer links with Industry and with mechanisms for improving Open Innovation
A major facet of this research involves characterising the amorphous form of drugs in isolation and within their dosage forms. An amorphous drug has a disordered structure, rapid dissolution and therefore has a higher bio-availability compared to its crystalline analogue.
The technical challenges required for analysing amorphous materials has lead to novel expertise in the area of screening poorly soluble drugs for potential development into amorphous medicines. Thermal analysis forms a strong theme throughout all of this work and so new applications and improvements on the state of the art are continuously being transferred into the research environment.
Dr Royall works within the Drug Delivery group which is a centre of expertise for the development of aerosol formulations and the analysis of the fate inhaled particles.
Forming respirable particles by either convergent (particle engineering) or divergent (milling) approaches often involves the formation and control of wholly or partially amorphous regions on the micron or nanometre scale. Thus his research directly impacts on the group’s output as it provides the means by which novel aerosol formulations maybe characterised and thus controlled.
Specific analytical expertise and capability:
- Dynamic mechanical analysis: Powder pocket, humidity control & immersion.
- Differential scanning calorimety
- Solution calorimetry
- Thermogravimetric analysis
- Hot stage microscopy
- Detection & quantification of amorphous / crystalline content
- Screens for amorphous medicine development
Other interests:
- Measuring the physical properties of chocolate
- Measuring the physical stability of drugs and medicines
- Characterising the dissolution of drug particles within lung fluids
Dr Jones defines a ‘dynamic formulation’ as one that changes either during or after dose actuation but, prior to deposition on the topical membrane. This process is often driven by volatile non-polar solvent systems in my research. Using dynamic drug delivery systems to administer therapeutic agents has a number of advantages, for example they can generate self-propulsion, supersaturation, phase changes and can provide a highly protective environment for therapeutic agents. Research projects are currently underway in the following areas:
- Supersaturated topical sprays for dermal drug delivery
- Collapsible foams systems for dermal drug delivery
- Microencapsulated nanoparticulate systems for administration to the lung and nose
- Cosmetically acceptable dermal nanoparticle formulations
- Self assembling patches for dermal delivery
