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Pharmaceutics and Pharmaceutical Chemistry – University of Reading

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  • Pharmaceutics and pharmaceutical chemistry PhD projects

    Ground-breaking pharmacy research

Pharmaceutics and Pharmaceutical Chemistry

If you want a career in pharmaceutics and pharmaceutical chemistry 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 Professor Vitaliy Khutoryanskiy by emailing v.khutoryanskiy@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 (such as cystic fibrosis). 

Advantage of this approach compared to, for example, enteric coating, is precision of drug release and efficacy, as the drug will be mixed with the carrier on a molecular level.  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 polymeric hydrotropes/co-crystals to improve aqueous drug solubility

With Dr Hisham Al-Obaidi

Hydrotrope is a molecule that possesses, just as surfactants do, both a very hydrophilic (water soluble) and hydrophobic (water insoluble) region.  When a hydrotrope is mixed with a poorly soluble drug, the hydrophobic region of the hydrotrope 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-crystal containing nanoparticles.  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 physioc-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.

Chemical proteomics probes for cysteine oxidation

With Dr Sarah Allman

The reversible oxidation of cysteine residues in proteins has been implicated in intracellular signalling events, activation of autophagy, protein folding and the maintenance of cellular redox balance. Oxidation reactions resulting in irreversible modifications are also associated with various disease states. As such, tools which allow us to identify proteins in the cell which are susceptible to oxidation have the potential to provide information about these processes. This interdisciplinary project brings together elements of synthetic chemistry, analytical sciences and cell biology. It focusses on the design and synthesis of molecule probes to react with the initial product of this oxidation reaction, and examine the ability of these compounds to label proteins contain cysteine residues susceptible to oxidation.

Design and synthesis of novel cellular imaging dyes

With Dr Sarah Allman

Within the cell, calcium ions act as a crucially important messenger, mediating a plethora of important signalling and signal transduction events. The ability to quantify and visualise the calcium status of the cell can therefore provide important insights into these pathways. Small molecule dyes which respond to the calcium status of the cell are often used to probe such events. As with all tools designed to probe biological systems, however, it is important they exert minimal adverse effects on the cell or influence the process under study. In this interdisciplinary project, you will use a combination of synthetic chemistry, analytical sciences and cell biology methods to design and test a series of novel indicator dyes designed to quantify cellular calcium signalling events whilst preserving normal cellular functions.

Integrated workflows for glycomics

With Dr Sarah Allman

Defects in protein post-translational modifications have been linked to a variety of disease states and developmental disorders. Glycosylation (the process by which carbohydrates are linked to the surface of biomolecules) is one of the most commonly observed protein modifications. Changes in both in the sugars displayed upon the surface of proteins and those released from cellular degradation pathways can provide insights into disease states, cellular metabolism and factors influencing protein catabolism. In this project, you will develop skills in synthetic chemistry, chemical biology and analytical sciences and use them to develop tools to enable the isolation and structural characterisation of sugars from different sources. You will then examine how these workflows can be adapted to facilitate functional characterisation of biologically relevant protein-carbohydrate binding interactions.

Structure and function of I-motif forming sequences

With Dr John Brazier

The i-motif is a four stranded structure formed by cytosine rich sequences of DNA. These sequences are found in a high proportion of gene promoter sequences and maybe useful as a target to modulate gene expression. The sequence composition of the i-motif forming sequence is crucial to the stability of the structure and potential for therapeutic action. The project will focus on probing the sequence composition of i-motif forming sequences, and linking sequence to stability and function.

Targeting triplet repeating nucleic acid sequences with DNA binding agents

With Dr John Brazier

Extended triplet repeat regions of DNA and RNA are associated with several diseases including Huntington's disease and myotonic dystrophy. In healthy human cells these repeat number in the 10s, but in a diseased state they number in the 100s-1000s. Targeting such long repeating sequences of DNA or RNA is very challenging, but could provide useful diagnostic information or therapeutic action. This project will investigate the use of bi-functional DNA binding molecules to cooperatively bind to repeating DNA sequence, and differentiate between different lengths of repeat.

Microbial detection using affordable microfluidic devices made from micro capillary film

With Dr Alexander Edwards

Background: Microfluidics and lab-on-a-chip

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.

The synthesis and analysis of novel anti-cancer agents: flavonoids

With Professor Helen Osborn

One of the major problems of cancer chemotherapy is that the drugs used have poor selectivities for cancer cells and cause damage to normal cells and organs. In recent years, flavonoids, a large class of natural products, have shown promising anticancer activities.

The aim of this project is to design and chemically synthesise a wide range of flavonoid derivatives and determine their anti-cancer activities and investigate key structural-activity parameters. Through this project you will gain expertise in advanced synthetic chemistry and analytical techniques as well as computational methods for drug design. 

The synthesis and analysis of novel anti-cancer agents: prodrugs for melanoma

With Professor Helen Osborn

One of the major problems of cancer chemotherapy is that the drugs used have poor selectivities for cancer cells and cause damage to normal cells and organs. For this reason, researchers have become interested in preparing non-toxic 'prodrugs' that are converted to the toxic drugs selectively at the tumour site, for example by enzymes that are only present at the tumour.

Within our group, we have expertise in developing prodrugs for melanoma and on this project you will have an opportunity to chemically synthesise targets that have been designed to be activated by the tyrosinase enzyme. These molecules will then be analysed using both chemical and enzymatic techniques to ascertain how the structural features of the prodrugs affect the release of the drug.

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.

Phytochemical and preclinical studies on medicinal plants

With Dr Katja Strohfeldt

Herbal and Complementary Medicines (HCM) is an area which is of growing importance to healthcare, so it is important to ensure that the products used fulfil the relevant quality standards. The aim of this project is to look at a range of selected plants, which are established or known for their traditional use in the treatment of infections, cancer or other relevant clinical issues to human health.

The research will include a full literature search, verification and extraction of plant material, full chemical analysis and the biological testing against a range of relevant bio-assays in order to understand their potential clinical application.

Within this project you will have the unique opportunity to work in a multidisciplinary team exploring new medicinal plants, studying their photochemistry and potential biological activity in order to establish quality standards for safe application.

Synthesis and evaluation of novel metal-based anti-cancer drugs

With Dr Katja Strohfeldt

Metal-based drugs form an important part of chemotherapy, with cisplatinum being involved in the treatment of over 50% of all solid tumours. The aim of this project is to synthesize a novel class of potential anti-cancer agents, which contain a range of body-own proteins.

This will allow us to circumvent two of the major drawbacks when using metal-based anti-cancer agents in a clinical setting: low aqueous solubility and low selectivity of the metal-based compound to the tumour tissue.

Within this project you will have the unique opportunity to work in a multidisciplinary team using new synthetic and analytical methodology, studying different drug delivery systems (formulation and analysis) and evaluating their cytotoxic profiles.

 

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