Darren Moss

Title: Lecturer in Pharmacology
Phone: 01782 734767
Email: d.moss1@keele.ac.uk
Location: Hornbeam Building, Room 2.26
Role: ISTM Research theme: Therapeutics
MPharm teaching
BSc (Hons) in Pharmaceutical Science, Technology and Business teaching
Contacting me: Try my office or arrange an appointment via e-mail
Darren Moss

Background

I graduated in Biological Science from Lancaster University in 2005 and worked for two and a half years in the drug discovery industry. I returned to education and completed my PhD in Pharmacology and Therapeutics from the University of Liverpool in 2012, working to understand the pharmacokinetics of antiretrovirals and other anti-infectives. I was employed for two and a half years at the Liverpool School of Tropical Medicine, working to develop novel treatments for tuberculosis, malaria and lymphatic filariasis. Following this, I moved back to the University of Liverpool to work on the development of novel in silico pharmacokinetic models, which were used to help optimise anti-infective treatment in patients. I also helped to develop and assess nanoformulations of currently used anti-retrovirals with the aim of improving oral bioavailability. I joined the School of Pharmacy as a lecturer in pharmacology in 2017. I teach on the MPharm and BSc courses and continue to undertake research in the areas of infectious diseases, nanopharmacology and pharmacokinetic modelling.

ISTM research theme Therapeutics

My current research focuses on four main themes:

 

1. Orally administered nanomedicine development

The delivery of therapeutic agents is characterised by numerous challenges including poor absorption, low penetration in target tissues and unspecific dissemination in organs, leading to toxicity or poor drug exposure. Several nanomedicine strategies have emerged as an advanced approach to enhance drug delivery and improve the treatment of several diseases. Nanoformulations can be effectively absorbed orally and subsequently concentrated in tissues through passive targeting, exploiting both the physicochemical characteristics of the nanocarriers and the specific properties of the tissues of interest. Additionally, different strategies can also be applied for active targeting of tissues, pathogens and cancer cells. Numerous processes mediate the pharmacokinetics of nanoformulations, with the absorption, distribution, metabolism and elimination (ADME) being poorly understood and often differing substantially from traditional formulations..Understanding how nanoformulation composition and physicochemistry influences drug distribution in the human body is of central importance when developing future treatment strategies. In my research I am working closely with the Keele Nanopharmaceutics group to establish nanomedicine “design blueprints” of property-pharmacokinetic relationships.

 

2. Pharmacokinetic modelling

Physiologically based pharmacokinetic (PBPK) modelling is a technique which aims to simulate pharmacokinetics in populations combining system data (e.g. demographics, physiology, anatomy and genetics) describing a population of interest and in vitro drug data (e.g. cell permeability, protein binding, intrinsic clearance, lipophilicity) through a mathematical description of absorption, distribution, metabolism and elimination(ADME).The PBPK approach can therefore be applied in investigating ‘what-if’ pharmacological and clinical scenarios such as drug-drug interactions, novel formulations, pharmacogenetics and the effect of comorbidities in different patient populations. I am currently developing novel PBPK models to help predict the exposure of antifungal and antibacterial treatments in humans, with the aim of optimising current treatment regimens in both adults and special populations.

 

3. Drug metabolism and drug transport

Drug metabolism and drug transport are affected by highly specialised proteins which are predominantly expressed within the intestine and gut. Collectively, these proteins regulate the bioavailability and clearance of drugs. In addition, many drug-drug interactions occur as a result of induction and/or inhibition of one or more of these proteins. My research involves the assessment of these interactions and how they may affect treatment success.

 

4. Drug discovery, drug development and pharmacology of infectious disease treatment

Neglected tropical diseases, in addition to the more widely funded disease malaria, are a diverse group of tropical infections which are especially common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens such as viruses, bacteria, protozoa and helminths. I am an affiliate of the Centre for Applied Entomology and Parasitology at Keele University and work closely with the group in the screening and pharmacokinetic evaluation of novel drug-based treatments for malaria and leishmaniasis. I continue to work closely with the Infection Pharmacology group at the University of Liverpool in the optimisation of HIV treatments. 

Selected Publications

  • Giardiello M, Liptrott NJ, McDonald T, Moss DM, Siccardi M, Martin P, Smith D, Gurjar R, Rannard S, Owen A. 2016. Accelerated discovery of oral nanomedicines: paediatric HIV nanotherapy translation from miniaturised screening to clinical production. Nature Communications, Article 13184. doi> link>
  • Moss DM, Liptrott NJ, Siccardi M, Owen A. 2015. Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter. Frontiers in Pharmacology. doi>
  • Moss DM and Siccardi M. 2014. Optimizing nanomedicine pharmacokinetics using physiologically based pharmacokinetics modelling. British Journal of Pharmacology, vol. 171(17), 3963-3979. doi>
  • Moss DM, Curley P, Shone A, Siccardi M, Owen A. 2014. A multisystem investigation of raltegravir association with intestinal tissue: implications for pre-exposure prophylaxis and eradication. Journal of Antimicrobial Chemotherapy, vol. 69(12), 3275-3281. doi> link>
  • Moss DM, Liptrott NJ, Curley P, Siccardi M, Back DJ, Owen A. 2013. Rilpivirine inhibits drug transporters ABCB1, SLC22A1, and SLC22A2 in vitro. Antimicrobial Agents and Chemotherapy, vol. 57(11), 5612-5618. doi> link>

Full Publications List show

Journal Articles

  • Moss DM, Curley P, Kinvig H, Hoskins C, Owen A. 2017. The biological challenges and pharmacological opportunities of orally administered nanomedicine delivery. Expert Rev Gastroenterol Hepatol, 1-14. link> doi>
  • Manzur A, Oluwasanmi A, Moss D, Curtis A, Hoskins C. 2017. Nanotechnologies in Pancreatic Cancer Therapy. Pharmaceutics, vol. 9(4). link> doi>
  • Curley P, Giardiello M, Liptrott NJ, Dickens D, Moss D, Hobson J, Savage AC, McDonald T, Siccardi M, Rannard S, Owen A. 2017. In vitro characterisation of solid drug nanoparticle compositions of efavirenz in a brain endothelium cell line. JOIN, vol. 2(3), 157-169. doi>
  • de Wolf E, Abdullah MI, Jones SM, Menezes K, Moss DM, Drijfhout FP, Hart SR, Hoskins C, Stronach EA, Richardson A. 2017. Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer. Sci Rep, vol. 7(1), 5410. link> doi>
  • Moss DM, Domanico P, Watkins M, Seonghee P, Randolph R, Wring S, Rajoli RKR, Hobson J, Rannard S, Siccardi M, Owen A. 2017. Simulating Intestinal Transporter and Enzyme Activity in a Physiologically Based Pharmacokinetic Model for Tenofovir Disoproxil Fumarate. Antimicrobial Agents and Chemotherapy. doi>
  • Hong WD, Gibbons PD, Leung SC, Amewu R, Stocks PA, Stachulski A, Horta P, Cristiano MLS, Shone AE, Moss D, Ardrey A, Sharma R, Warman AJ, Bedingfield PTP, Fisher NE, Aljayyoussi G, Mead S, Caws M, Berry NG, Ward SA, Biagini GA, O'Neill PM, Nixon GL. 2017. Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis. J Med Chem, vol. 60(9), 3703-3726. link> doi>
  • Curley P, Rajoli RK, Moss DM, Liptrott NJ, Letendre S, Owen A, Siccardi M. 2016. Efavirenz Is Predicted To Accumulate in Brain Tissue: an In Silico, In Vitro, and In Vivo Investigation. Antimicrobial Agents and Chemotherapy. doi>
  • Giardiello M, Liptrott NJ, McDonald T, Moss DM, Siccardi M, Martin P, Smith D, Gurjar R, Rannard S, Owen A. 2016. Accelerated discovery of oral nanomedicines: paediatric HIV nanotherapy translation from miniaturised screening to clinical production. Nature Communications, Article 13184. doi> link>
  • Curley P, Moss D, Siccardi M, Owen A. 2016. Development and Validation of a LC-MS/MS Assay for the Quantification Of Efavirenz In Different Biological Matrices. Bioanalysis. doi>
  • Moss DM, Marzolini C, Rajoli RK, Siccardi M. 2015. Applications of physiologically based pharmacokinetic modeling for the optimization of anti-infective therapies. Expert Opinion on Drug Metabolism and Toxicology, vol. 11(8), 1203-1217. doi>
  • Moss DM, Liptrott NJ, Siccardi M, Owen A. 2015. Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter. Frontiers in Pharmacology. doi>
  • Capper MJ, O'Neil PM, Fisher N, Strange RW, Moss DM, Ward SA, Biagini GA, Antonyuk SV. 2015. Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1. Proceedings of the National Academy of Sciences. doi>
  • Moss DM, Neary M, Owen A. 2014. The role of drug transporters in the kidney: lessons from tenofovir. British Journal of Pharmacology, vol. 5. doi>
  • Moss DM and Siccardi M. 2014. Optimizing nanomedicine pharmacokinetics using physiologically based pharmacokinetics modelling. British Journal of Pharmacology, vol. 171(17), 3963-3979. doi>
  • Moss DM, Curley P, Shone A, Siccardi M, Owen A. 2014. A multisystem investigation of raltegravir association with intestinal tissue: implications for pre-exposure prophylaxis and eradication. Journal of Antimicrobial Chemotherapy, vol. 69(12), 3275-3281. doi> link>
  • Moss DM, Liptrott NJ, Curley P, Siccardi M, Back DJ, Owen A. 2013. Rilpivirine inhibits drug transporters ABCB1, SLC22A1, and SLC22A2 in vitro. Antimicrobial Agents and Chemotherapy, vol. 57(11), 5612-5618. doi> link>
  • Siccardi M, Rajoli RKR, Curley P, Olagunju A, Moss DM, Owen A. 2013. Physiologically-based pharmacokinetic models for the optimisation of antiretroviral therapy: recent progress and future perspectives. Future Virology. doi>
  • Liptrott NJ, Curley P, Moss DM, Back DJ, Khoo SH, Owen A. 2013. Interactions between tenofovir and nevirapine in CD4+ T cells and monocyte-derived macrophages restrict their intracellular accumulation. Journal of Antimicrobial Chemotherapy. doi>
  • Moss DM, Siccardi M, Back DJ, Owen A. 2013. Predicting intestinal absorption of raltegravir using a population-based ADME simulation. Journal of Antimicrobial Chemotherapy, vol. 68(7), 1627-1634. doi> link>
  • Nixon G, Moss DM, Shone A, Lalloo D, Fisher N, O'Neill P, Ward S, Biagini G. 2013. Antimalarial pharmacology and therapeutics of atovaquone. Journal of Antimicrobial Chemotherapy. doi>
  • Warman A, Rito T, Fisher N, Moss DM, Berry N, O'Neill P, Ward S, Biagini G. 2012. Antitubercular pharmacodynamics of phenothiazines. Journal of Antimicrobial Chemotherapy. doi>
  • Siccardi M, D'Avolio A, Rodriguez-Novoa S, Cuenca L, Simiele M, Baietto L, Calgagno A, Moss D, Bonora S, Soriano V, Back DJ, Owen A, Di Perri G. 2012. Intrapatient and interpatient pharmacokinetic variability of raltegravir in the clinical setting. Therapeutic Drug Monitoring. doi>
  • Moss DM, Siccardi M, Murphy M, Piperakis MM, Khoo SH, Back DJ, Owen A. 2012. Divalent metals and pH alter raltegravir disposition in vitro. Antimicrobial Agents and Chemotherapy, vol. 56(6), 3020-3026. doi> link>
  • Moss DM, Kwan WS, Liptrott NJ, Smith DL, Siccardi M, Khoo SH, Back DJ, Owen A. 2011. Raltegravir is a substrate for SLC22A6: A putative mechanism for the interaction between raltegravir and tenofovir. Antimicrobial Agents and Chemotherapy, vol. 55(2), 879-887. doi> link>
  • Siccardi M, D'Avolio A, Nozza S, Simiele M, Baietto L, Stefani FR, Moss D, Kwan WS, Castagna A, Lazzarin A, Calgango A, Bonora S, Back DJ, Di Perri G, Owen A. 2010. Maraviroc is a substrate for OATP1B1 in vitro and maraviroc plasma concentrations are influenced by SLCO1B1 521 T>C polymorphism. Pharmacogenetics and Genomics. doi>

Chapters

  • McDonald T, Siccardi M, Moss D, Liptrott N, Giardiello M, Owen A. 2015. The Application of Nanotechnology to Drug Delivery in Medicine. In Nano Engineering: Global Approaches to Health and Safety Issues. (3 vols.). Elsevier Health Sciences.

Other

  • Roberts O, Curley P, Rajoli RKR, Moss DM, Lamorde M, Owen A, Scarsi KK, Siccardi M. 2017. An in vitro-in silico study of reduced-dose efavirenz interaction with levonorgestrel.
  • Savage AC, Chadwick SJ, Moss DM, Box H, Livermore J, Owen A, Rannard S. 2017. Formulation of antiretroviral drugs into single and dual component solid drug nanoparticles for improved oral bioavailability.
  • Moss DM, Rajoli RKR, Curley P, Owen A, SIccardi M. 2016. The development of a physiologically based pharmacokinetic rat model for simulating absorption, distribution and elimination of pharmacological compounds. Oral presentation, SEB symposium on improving experimental approaches in animal biology: Implementing the 3Rs, London.
  • Curley P, Rajoli RKR, Moss DM, Hobson JJ, Freel Meyers CL, Flexner CW, Rannard SP, Owen A, Siccardi M. 2016. In Silico pharmacokinetic/pharmacodynamic simulation of long acting tenofovir injectable formulation for pre exposure prophylaxis strategies.
  • Moss DM, Siccardi M, Owen A. 2015. Protein binding in combination with pH, metals and interacting drugs can augment the disposition of raltegravir.
  • Moss DM, Hobson J, Domanico P, Watkins M, Park S, Randolph R, Owen A, Siccardi M. 2015. Modelling transporter and enzyme inhibition for increased bioavailability of tenofovir disoproxil fumarate.
  • Moss DM, Liptrott NJ, Siccardi M, Owen A. 2015. Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter.
  • SIccardi M, Moss DM, Rajoli R, Giardiello M, McDonald T, Liptrott NJ, Martin P, Rannard S, Owen A. 2014. Prediction of nanoparticle distribution through physiologically based pharmacokinetic modelling.
  • Moss DM, Curley P, Shone A, Siccardi M, Owen A. 2014. A multi-system investigation of the mechanisms for raltegravir association with intestinal tissue after oral administration.
  • Moss DM, Siccardi M, Khoo SH, Back DJ, Owen A. 2012. Development of a population-based ADME simulation to assess variability in raltegravir pharmacokinetics.
  • Moss DM, Siccardi M, Khoo SH, Back DJ, Owen A. 2012. The interplay between raltegravir solubility, tablet dissolution, metal binding, charge state and cell permeability.
  • Moss DM, Siccardi M, Khoo SH, Back DJ, Owen A. 2012. Interactions of Rilpivirine with Drug Transporters in vitro.
  • Moss D, Murphy M, Back DJ, Owen A. 2011. Magnesium inhibits raltegravir cell membrane permeability: elucidating the interaction between raltegravir and antacids in vivo. Oral presentation, 17th International Conference on Cytochrome P450, Manchester UK.
  • Moss D, Murphy M, Siccardi M, Khoo S, Back DJ, Owen A. 2011. Influence of pH on Transcellular Permeability of Raltegravir: Unravelling the Interaction with Antacids and Food.
  • Moss D, Liptrott N, Khoo SH, Back DJ, Owen A. 2010. Influence of SLC22A6 by antiretroviral drugs: potential for drug-drug interactions in patients.
  • Moss D, Liptrott N, Khoo S, Back DJ, Owen A. 2010. Inhibition of SLCO22A1 by antiretroviral drugs: potential for drug-drug interaction in patients. Oral presentation, 7th Annual PRISM conference, Lancaster UK.
  • Liptrott N, Curley P, Moss D, Back DJ, Owen A, Khoo S. 2010. Interactions between Tenofovir (TFV) and Nevirapine (NVP) in CD4+ T cells and Monocyte Derived Macrophages Restrict their Intracellular Accumulation.
  • Else L, Liptrott N, Moss D, Dutton J, Fraser W, Kakude T, Mrus J, Back DJ. 2010. Evaluating the effect of gender on darunavir and ritonavir exposure in HIV infected subjects (a post-hoc analysis of the GRACE PK sub-study).
  • Moss D, Kwan WS, Liptrott N, SIccardi M, Smith D, Khoo SH, Back DJ, Owen A. 2010. Raltegravir is a substrate for the influx transporters OAT1 and PEPT1 and the efflux transporter Pgp but is not transported by OATP1A2, OATP1B1, OATP1B3, OCT1, NTCP, or PEPT2.
  • Moss D, Siccardi M, Kwan WS, D'Avolio A, Bonora S, Khoo S, Back DJ, Di Perri G, Owen A. 2010. Solute carrier organic anion transporter 1B1 (SLCO1B1) mediates transport of maraviroc using a X. leavis model.
  • Moss D, Siccardi M, D'Avolio A, Nozza S, Bonora S, Castagna A, Baietto L, Stefani FR, Moss D, Calcagno A, Scinadra M, Lazzarin A, Back DJ, Owen A, Di Perri G. 2009. Is maraviroc a substrate for SLCO1B1?.
  • Kwan WS, Moss D, Hartkoorn R, Salcedo-Sora E, Bray P, Khoo S, Back DJ, Owen A. 2008. Determining the substrate specificity of SLCO1B3 for antiretroviral drugs using a X. laevis model.
  • Southall R, Shaw L, Dilworth C, Moss D, Little C, Butler P, Dykstra P, Gill H. 2007. Development of a high throughput assay for the screening of mechanism-based cytochrome P450 inhibition.

I teach elements of the undergraduate curriculums offered at the Keele School of Pharmacy (Master in Pharmacy (Hons) and BSc (Hons) in Pharmaceutical Science, Technology and Business).

I welcome applications from students who wish to undertake PhD postgraduate studies. Interested students can contact me directly on d.moss1@keele.ac.uk to discuss potential projects as well as the application process