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If you want a career in pharmaceutics research, joining a PhD project at the Reading School of Pharmacy will put you on the right path. 

This is a taster of some of the PhD projects you can be involved in at the University of Reading. To discuss the different projects available, please contact Dr Graeme Cottrell by emailing g.s.cottrell@reading.ac.uk.


EXPLORATION OF NOVEL DRUG-EXCIPIENT COMPLEXES FOR ENHANCED PULMONARY DRUG DELIVERY

With Dr Hisham Al-Obaidi

Delivery to lungs has always been a challenging task where the drug particles need to be delivered deep in the alveoli. Using molecular mixtures of drug-carrier can achieve unique control over drug release and can be used to release the drug at site of action.

Advantage of this approach is precision of drug release and potential to deliver large doses of the drug. Using spray drying to form these complexes means these can be easily scaled up to prepare larger quantities. The drug-excipients solutions will then be spray dried using different pressures and temperatures based on evaporation temperature and solvents vapour pressure.

This will be followed by characterization of the formed particles using XRPD, DSC, FTIR, solid state NMR, Raman and FTIR. In-vitro dissolution experiments will also be carried out to study dissolution rates and to measure drug solubility at different pH values.


THE USE OF HYBRID CO-AMORPHOUS POLYMERIC DISPERSIONS TO IMPROVE AQUEOUS DRUG SOLUBILITY

With Dr Hisham Al-Obaidi

Amorphous solid dispersions (can also be combined with co-amorphous dispersions) can be used to enhance the solubility of hydrophobic drugs. When a polymeric molecule is mixed with a poorly soluble drug, the hydrophobic region of the polymer it thought to associate with the comparable region of the poorly soluble drug, resulting in a dramatic enhancement of the drugs solubility in water.

A combination of advanced physico-chemical techniques will be used to gain the required understanding of the preparation of the novel co-amorphous dispersions. The mechanism for enhanced solubility of drug will be determined using a combination of advanced physico-chemical techniques, in particular light and small angle neutron scattering (SANS). The resulting nanoparticle formulations will be characterized in detail in respect to their physico-chemical properties.

For example their moisture content will be determined using thermogravimetric analysis (TGA), x-ray powder diffraction (XRPD) and FTIR will be used to characterize the physical state of the components of the nanoparticles, while scanning and transmission electron microscopy will be used to assess the shape and surface texture of the particles and nuclear magnetic resonance (NMR) will allow the study of the molecular interactions between components.


MICROBIAL DETECTION USING AFFORDABLE MICROFLUIDIC DEVICES MADE FROM MICRO CAPILLARY FILM

With Dr Alexander Edwards

A major aim of microfluidics is to develop miniature version of clinical diagnostic tests. We developed a new type of microfluidics that promises to deliver microfluidic properties with the simplicity and low cost of a dipstick (Reis et al Lab Chip 2016). This new project will focus on clinical application of microbial detection and aims to deliver fully functioning devices for detecting harmful and infectious bacteria and to profile antibiotic resistance in a smartphone-friendly, low-cost dipstick format.

NANOTECHNOLOGIES AS TOOLS FOR SELECTIVE MODULATION OF THE DOPAMINERGIC SYSTEM

With Dr Francesca Greco

Dopamine is a key neurotransmitter, involved in many physiological process including voluntary movement and reward.

The project will look at using nanotechnologies applied to agonists and antagonists of the dopamine receptors, to produce localized and selective activation (or inhibition) of the dopaminergic systems. This approach can potentially have therapeutic applications for diseases associated with an impairment of the dopaminergic tone.


PRODRUGS FOR TARGETING CANCER 

With Dr Francesca Greco

This project will focus on the development of new therapeutics for cancer which are proposed to have fewer side effects than current clinical therapies.

In recent years, low molecular weight prodrugs and macromolecular prodrugs (nanotechnologies) have been suggested as tools to increase the selectivity of cancer treatment and these molecules will therefore be the focus of this programme. The aim of this project is therefore to prepare, purify and analyse new prodrugs, designed for specific activation at the tumour.

The prodrug system will be inactive when administered but it will become active after exposure to specific triggers present at the tumour site (e.g. enzymes). This is a highly interdisciplinary project which will involve the design and chemical synthesis of these target compounds as well as their biological evaluation.


ANTIMICROBIAL PEPTIDES AS EFFECTIVE THERAPEUTIC AGENTS

With Professor Rebecca Green

Antimicrobial peptides have potential roles in fighting infection and disease due to their ability to target specific lipid properties of cell membranes. AMPs have potential as future therapeutic agents helping to overcome current problems such as antimicrobial resistance or poor side effect profiles of conventional therapies. 

However, the fact that the mechanism of action of AMPs remain poorly understood, and that there are difficulties in terms of stability and controlling cell selectivity and potency, currently limit their use. Professor Green has a number of PhD and MSc research projects available in the area of antimicrobial protein and peptides and their potential use as antimicrobials and anticancer agents. Her research uses a number of analytical methodologies (spectroscopic and calorimetric), and large-scale central neutron reflectometry facilities. 

Other areas where Professor Green has projects available include: 

  • Investigations linked to understanding how lipid composition in biological membranes plays a role in cellular activity
  • Investigations looking at polyphenols/tannins binding to proteins and lipids, and how these interactions impact on nutritional properties.

DEVELOPING NOVEL POLYMERS AND NANOMATERIALS FOR TRANSMUCOSAL DRUG DELIVERY

With Professor Vitaliy Khutoryanskiy

Mucoadhesion is the ability of pharmaceutical materials to adhere to mucosal tissues in the human body and provide temporary retention. This property has been widely used to develop polymeric dosage forms for buccal, oral, nasal, ocular, intravesical and vaginal drug delivery.

This research project will be aimed at the development of novel mucoadhesive polymers and nanomaterials, studies of their interactions with the components of the mucus gel in solutions by various physicochemical techniques, characterisation of their adhesive properties with respect to biological and model substrates, formulation of mucoadhesive dosage forms and their in vitro evaluation.


MICROENCAPSULATED PROBIOTICS FOR ORAL DELIVERY

With Professor Vitaliy Khutoryanskiy and Dr Dimitris Charalampopoulos

Probiotics are live bacteria that reside in human intestinal tract and provide numerous beneficial effects. Oral delivery of probiotics is viewed as an efficient therapeutic strategy to improve gut health.

This project will be focused on the development of microencapsulated forms of live probiotic bacteria that will facilitate their survival during transit through the low pH of the stomach, when administered via oral route. This highly interdisciplinary project will provide an excellent training opportunity in microencapsulation technologies, microbiological methods and formulation science.


ACTIVE USE OF H-BOND PROPENSITY DATA IN CRYSTAL STRUCTURE DETERMINATION

With Dr Kenneth Shankland

The Cambridge Structural Database (CSD) is a tremendous resource for structural chemists, allowing them to search for existing structures and mine the database for a variety of information.  Recently, CSD software has been developed that allows one to predict the propensity of certain functional groups to form H-bonds with other moieties in crystals. This project will investigate the use of structural constraints, derived from H-bond propensity calculations, in the crystal structure determination of molecular materials using powder X-ray diffraction.

QUANTITATIVE PHASE ANALYSIS AND AMORPHOUS MATERIAL CHARACTERISATION

With Dr Kenneth Shankland

Powder X-ray diffraction is a powder tool for the quantitative analysis of crystalline materials in the solid state, and can also be used to quantify amounts of amorphous materials. This project will apply recent developments in powder X-ray data analysis (specifically, quantitative Rietveld and pair distribution function techniques) to the analysis and characterisation of materials of pharmaceutical interest, linking results to observed physical properties.

USING DFT-D CALCULATIONS TO VERIFY COMPLEX MOLECULAR CRYSTAL STRUCTURES

With Dr Kenneth Shankland

Dispersion-corrected density functional theory (DFT-D) calculations find great utility in the field of crystal structure prediction but are also increasingly being used in the verification of crystal structures. This research project is aimed at studying the applicability of DFT-D to moderately complex molecular systems where structural ambiguities exist. The project will involve mostly computational work but also both practical powder X-ray diffraction.

TOPICAL AND TRANSDERMAL DRUG DELIVERY

With Professor Adrian Williams     

Drug delivery to and through the skin is attractive to treat local skin conditions such as psoriasis and eczema and to deliver drug to the systemic circulation whilst avoiding first pass metabolism. However, human skin is a remarkable barrier designed to "keep the outsides out and insides in" and this severely limits the range and dose of therapeutic agents that can be delivered via topical administration. 

Research projects aim to develop novel delivery systems and formulations to overcome the barriers to drug delivery into and through skin. Approaches vary and include: 

  • Manipulating the thermodynamic activity of a drug when a formulation is applied to the skin, for example generating supersaturated systems.
  • Exploiting the pathophysiology of skin diseases to trigger drug release from a formulation to target the affected site, for example applying a drug in a pH responsive carrier particle to sites of active atopic dermatitis
  • Targeting drug delivery to hair follicles using novel nanoparticles
  • Using microneedle arrays which penetrate the outer skin barrier but do not reach down to the pain receptors to broach the skin barrier, allowing delivery of macromolecular drugs.

All projects provide broad training ranging from the biology and biophysics of skin through to physical chemistry of formulation design, development and evaluation. Most projects also collaborate with end users including patients, clinicians and pharmaceutical and cosmetic companies.

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