Martin Luther University Halle-Wittenberg

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Head of the group

(Foto: Maike Glöckner)

(Foto: Maike Glöckner)

(Foto: Maike Glöckner)

Prof. Dr. Lea Ann Dailey

Pharmaceutical Technology and Biopharmaceutics
Biopharmacy group

Floor 1 - Room 139
Wolfgang-Langenbeck-Str. 4
06120 Halle (Saale)

phone: +49 (0) 345 55-25000
fax: +49 (0) 345 55-27292
mail:

Nanomedicines and Nanodiagnostics Research Themes

My research interests focus on the development of novel nanoformulations for pulmonary drug delivery12-29. I was one of the first researchers to investigate the toxicology of biodegradable polymer nanoparticles in the lung25, a study which merged my interests in nanotoxicology and nanomedicine research. At King’s College London, we assessed the in vivo biocompatibility of a range of drug carrier systems in the lung, whereby a number of exciting achievements were made. We were able to correlate nanoparticle surface hydrophobicity with acute lung inflammation18 and using metabolomics identified adenosine monophosphate as a putative soluble biomarker of nanoparticle-induced neutrophilic inflammation17.  We also identified albumin-based nanoparticles and lipid nanocapsules (LNC) as materials that are particularly well-tolerated in the lung, even at high concentrations. Using longitudinal SPECT-CT imaging, we could show that LNC exhibited a half-life of ~10 h in the murine lung13, in contrast to albumin-based systems with a much longer half-life of ~96 h (figure 1)15. This work has led directly to two current projects investigating different nanocarrier systems for inhaled tuberculosis treatment with benzothiazinones, a class of anti-mycobacterial drug compounds. It also led another current project investigating alveolar macrophage responses to inhaled poorly soluble drug compounds and the development of a high-content in vitro screen designed to predict problematic compound-induced foamy macrophage development. This work is funded by the UK NC3R and Germany’s Stiftung set, with sponsorship from GSK, Pfizer, AstraZeneca, and Envigo.

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Nanodiagnostics

In 2013, I began a fruitful collaboration with the Division of Imaging Sciences at King’s College London, utilising my expertise in nanotoxicology to assess the biocompatibility of photoluminescent p-conjugated polymers as safer alternatives to quantum dots for optical imaging applications1-11. Initially a side project, this research theme rapidly expanded to encompass roughly half of my current research activities. In this field we have been able improve formulation design for novel near-infrared emitting conjugated polymers (abbr. P3/P4, figure 2)1, establish a microfluidics-based manufacturing method for conjugated polymers encapsulated in biodegradable nanocarrier systems2, and assess the biocompatibility of a wide range of nanodiagnostics4-9. In addition to investigating p-conjugated polymer nanoparticles for clinical use, we are also assessing whether they can be used to enhance the signal detection limits of lateral flow immunoassay assays for ex vivo diagnostic applications10.

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Full publication list grouped by research themes

Publications: Nanodiagnostics

(1) Crossley, D.L., Urbano, L., Neumann, R., Bourke, S., Jones, J., Dailey, L.A., Green, M., Humphries, M.J., King, S.M., Turner, M.L., Ingleson, M.J. Post-polymerization C-H Borylation of Donor-Acceptor Materials Gives Highly Efficient Solid State Near-Infrared Emitters for Near-IR-OLEDs and Effective Biological Imaging (2017) ACS Appl Mat Interf, 9 (34), 28243-28249.

(2) Abelha, T.F., Phillips,   T.W., Bannock, J.H., Nightingale, A.M., Dreiss, C.A., Kemal, E., Urbano, L.,   Demello, J.C., Green, M., Dailey,   L.A.* Bright conjugated polymer nanoparticles containing a biodegradable   shell produced at high yields and with tuneable optical properties by a   scalable microfluidic device (2017) Nanoscale, 9 (5), 2009-2019.

(3) Kemal, E., Abelha, T.F., Urbano, L., Peters, R.,   Owen, D.M., Howes, P., Green, M., Dailey,   L.A.* Bright, near infrared emitting PLGA-PEG dye-doped CN-PPV   nanoparticles for imaging applications (2017) RSC Advances, 7 (25),   15255-15264.

(4) Taniguchi, S., Sandiford, L., Cooper, M., Rosca, E.V., Ahmad Khanbeigi, R., Fairclough, S.M., Thanou, M., Dailey, L.A., Wohlleben, W., Von Vacano, B., TMDe Rosales, R., Dobson, P.J., Owen, D.M., Green, M. Hydrophobin-Encapsulated Quantum Dots (2016) ACS Appl. Mater. Interf., 8 (7), 4887-4893.

(5) Green, M., Haigh, S.J., Lewis, E.A., Sandiford, L., Burkitt-Gray, M., Fleck, R., Vizcay-Barrena, G., Jensen, L., Mirzai, H., Curry, R.J., Dailey, L.-A. The Biosynthesis of Infrared-Emitting Quantum Dots in Allium Fistulosum (2016) Sci. Rep. 6,  20480.

(6) Peters, R., Sandiford, L., Owen, D.M., Kemal, E., Bourke, S., Dailey, L.A., Green, M. Red-emitting protein-coated conjugated polymer nanoparticles (2016) Photochem. Photobiol. Sci., 15 (11), 1448-1452.

(7) Khanbeigi, R.A., Hashim, Z., Abelha, T.F., Pitchford, S., Collins, H., Green, M., Dailey, L.A.* Interactions of stealth conjugated polymer nanoparticles with human whole blood (2015) J. Mater. Chem. B, 3 (12), 2463-2471.

(8) Ahmad Khanbeigi, R., Abelha, T.F., Woods, A., Rastoin, O., Harvey, R.D., Jones, M.-C., Forbes, B., Green, M.A., Collins, H., Dailey, L.A. Surface Chemistry of Photoluminescent F8BT Conjugated Polymer Nanoparticles Determines Protein Corona Formation and Internalization by Phagocytic Cells (2015) Biomacromol., 16 (3), 733-742.

(9) Hashim, Z., Green, M., Chung, P.H., Suhling, K., Protti, A., Phinikaridou, A., Botnar, R., Khanbeigi, R.A., Thanou, M., Dailey, L.A., Commander, N.J., Rowland, C., Scott, J., Jenner, D. Gd-containing conjugated polymer nanoparticles: Bimodal nanoparticles for fluorescence and MRI imaging (2014) Nanoscale, 6 (14), 8376-8386.

(10) Wiriyachaiporn, S., Howarth, P.H., Bruce, K.D., Dailey, L.A.* Evaluation of a rapid lateral flow immunoassay for Staphylococcus aureus detection in respiratory samples (2013) Diagn. Microbiol. Infect. Dis., 75 (1), 28-36.

(11) Stürzenbaum, S.R., Höckner, M., Panneerselvam, A., Levitt, J., Bouillard, J.-S., Taniguchi, S., Dailey, L.-A., Khanbeigi, R.A., Rosca, E.V., Thanou, M., Suhling, K., Zayats, A.V., Green, M. Biosynthesis of luminescent quantum dots in an earthworm (2013) Nature Nanotechnol., 8 (1), 57-60.

Publications: Inhaled Nanomedicines

(12) Kumar, A., Bicer, E.M., Pfeffer, P., Monopoli, M.P., Dawson, K.A., Eriksson, J., Edwards, K., Lynham, S., Arno, M., Behndig, A.F., Blomberg, A., Somers, G., Hassall, D., Dailey, L.A., Forbes, B., Mudway, I. Differences in the coronal proteome acquired by particles depositing in the lungs of asthmatic versus healthy humans (2017) Nanomedicine, 13 (8), 2517-2521.

(13) Patel, A., Woods, A., Riffo-Vasquez, Y., Babin-Morgan, A., Jones, M.-C., Jones, S., Sunassee, K., Clark, S., De Rosales, R.T.M., Page, C., Spina, D., Forbes, B., Dailey, L.A.* Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration (2016) J. Control. Rel., 235, 24-33.

(14) Kumar, A., Bicer, E.M., Morgan, A.B., Pfeffer, P.E., Monopoli, M., Dawson, K.A., Eriksson, J., Edwards, K., Lynham, S., Arno, M., Behndig, A.F., Blomberg, A., Somers, G., Hassall, D., Dailey, L.A., Forbes, B., Mudway, I.S. Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid (2016) Nanomedicine, 12 (4), 1033-1043.

(15) Woods, A., Patel, A., Spina, D., Riffo-Vasquez, Y., Babin-Morgan, A., De Rosales, R.T.M., Sunassee, K., Clark, S., Collins, H., Bruce, K., Dailey, L.A.*, Forbes, B. In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for pulmonary drug delivery (2015) J. Control. Rel., 210, 7685, 1-9.

(16) Kumar, A., Forbes, B., Mudway, I., Bicer, E.M., Dailey, L.A.* What are the biological and therapeutic implications of biomolecule corona formation on the surface of inhaled nanomedicines? (2015) Nanomed., 10 (3), 343-345.

(17) Dailey, L.A.*, Hernández-Prieto, R., Casas-Ferreira, A.M., Jones, M.-C., Riffo-Vasquez, Y., Rodríguez-Gonzalo, E., Spina, D., Jones, S.A., Smith, N.W., Forbes, B., Page, C., Legido-Quigley, C. Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity (2015) Nanotoxicol., 9 (1), 106-115.

(18) Jones, M.-C., Jones, S.A., Riffo-Vasquez, Y., Spina, D., Hoffman, E., Morgan, A., Patel, A., Page, C., Forbes, B., Dailey, L.A.* Quantitative assessment of nanoparticle surface hydrophobicity and its influence on pulmonary biocompatibility (2014) J. Control. Rel., 183 (1), 94-104.

(19) Kumar, A., Dailey, L.A., Forbes, B. Lost in translation: What is stopping inhaled nanomedicines from realizing their potential? (2014) Ther. Deliv., 5 (7), 757-761.

(20) Jones, M.C., Kumar, A., Spina, D., Forbes, B., Page, C., Dailey, L.A.* In vivo safety and particokinetics of inhaled nanomedicines (2011) J. Drug Del. Sci. Tech., 21 (4), 339-346.

(21) Gul, M.O., Jones, S.A., Dailey, L.A., Nacer, H., Ma, Y., Sadouki, F., Hider, R., Araman, A., Forbes, B. A poly(vinyl alcohol) nanoparticle platform for kinetic studies of inhaled particles (2009) Inhal. Toxicol., 21 (7), 631-640.

(22) Kleemann, E., Jekel, N., Dailey, L.A., Roesler, S., Fink, L., Weissmann, N., Schermuly, R., Gessler, T., Schmehl, T., Roberts, C.J., Seeger, W., Kissel, T. Enhanced gene expression and reduced toxicity in mice using polyplexes of low-molecular-weight poly(ethylene imine) for pulmonary gene delivery (2009) J. Drug Targ., 17 (8), 638-651.

(23) Salem, L.B., Bosquillon, C., Dailey, L.A., Delattre, L., Martin, G.P., Evrard, B., Forbes, B. Sparing methylation of β-cyclodextrin mitigates cytotoxicity and permeability induction in respiratory epithelial cell layers in vitro (2009) J. Control. Rel., 136 (2), 110-116.

(24) Grenha, A., Grainger, C.I., Dailey, L.A., Seijo, B., Martin, G.P., Remuñán-López, C., Forbes, B. Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro (2007) Eur. J. Pharm. Sci., 31 (2), 73-84.

(25) Dailey, L.A.*, Jekel, N., Fink, L., Gessler, T., Schmehl, T., Wittmar, M., Kissel, T., Seeger, W. Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung (2006) Toxicol. Appl. Pharmacol., 215 (1), 100-108.

(26) Dailey, L.A., Kleemann, E., Merdan, T., Petersen, H., Schmehl, T., Gessler, T., Hänze, J., Seeger, W., Kissel, T. Modified polyethylenimines as non-viral gene delivery systems for aerosol therapy: Effects of nebulization on cellular uptake and transfection efficiency (2004) J. Control. Rel., 100 (3), 425-436.

(27) Kleemann, E., Dailey, L.A., Abdelhady, H.G., Gessler, T., Schmehl, T., Roberts, C.J., Davies, M.C., Seeger, W., Kissel, T. Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: Investigations of the complex structure and stability during air-jet and ultrasonic nebulization (2004) J. Control. Rel., 100 (3), 437-450.

(28) Dailey, L.A., Kleemann, E., Wittmar, M., Gessler, T., Schmehl, T., Roberts, C., Seeger, W., Kissel, T. Surfactant-Free, Biodegradable Nanoparticles for Aerosol Therapy Based on the Branched Polyesters, DEAPA-PVAL-g-PLGA (2003) Pharm. Res., 20 (12), 2011-2020.

(29) Dailey, L.A., Schmehl, T., Gessler, T., Wittmar, M., Grimminger, F., Seeger, W., Kissel, T. Nebulization of biodegradable nanoparticles: Impact of nebulizer technology and nanoparticle characteristics on aerosol features (2003) J. Control. Rel., 86 (1), 131-144.

Publications: Inhalation Translation

(30) Guillon, A., Sécher, T., Dailey, L.A., Vecellio, L., de Monte, M., Si-Tahar, M., Diot, P., Page, C.P., Heuzé-Vourc'h, N. Insights on animal models to investigate inhalation therapy: Relevance for biotherapeutics (2018) Int J Pharm, 536 (1), 116-126.

(31) Hoffman, E., Patel, A., Ball, D., Klapwijk, J., Millar, V., Kumar, A., Martin, A., Mahendran, R., Dailey, L.A., Forbes, B., Hutter, V. Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis (2017) Pharm Res, 34 (12), 2466-2476.

(32) Kumar, A., Dailey, L.A., Swedrowska, M., Siow, R., Mann, G.E., Vizcay-Barrena, G., Arno, M., Mudway, I.S., Forbes, B. Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels (2016) FEBS Letters, 590 (2), 258-269.

(33) Hoffman, E., Kumar, A., Kanabar, V., Arno, M., Preux, L., Millar, V., Page, C., Collins, H., Mudway, I., Dailey, L.A.*, Forbes, B. In Vitro Multiparameter Assay Development Strategy toward Differentiating Macrophage Responses to Inhaled Medicines (2015) Mol. Pharm., 12 (8), 2675-2687.

(34) Haddrell, A.E., Davies, J.F., Miles, R.E.H., Reid, J.P., Dailey, L.A., Murnane, D. Dynamics of aerosol size during inhalation: Hygroscopic growth of commercial nebulizer formulations (2014) Int. J. Pharm., 463 (1), 50-61.

(35)   Forbes, B., O'Lone, R., Allen, P.P., Cahn, A., Clarke, C., Collinge, M., Dailey, L.A., Donnelly, L.E., Dybowski, J., Hassall, D., Hildebrand, D., Jones, R., Kilgour, J., Klapwijk, J., Maier, C.C., McGovern, T., Nikula, K., Parry, J.D., Reed, M.D., Robinson, I., Tomlinson, L., Wolfreys, A. Challenges for inhaled drug discovery and development: Induced alveolar macrophage responses (2014) Adv. Drug Del. Rev., 71, 15-33.

(36) Forbes, B., Asgharian, B., Dailey, L.A., Ferguson, D., Gerde, P., Gumbleton, M., Gustavsson, L., Hardy, C., Hassall, D., Jones, R., Lock, R., Maas, J., McGovern, T., Pitcairn, G.R., Somers, G., Wolff, R.K. Challenges in inhaled product development and opportunities for open innovation (2011) Adv. Drug Del. Rev., 63 (1-2), 69-87.

(37) Van Den Bogaard, E.H.J., Dailey, L.A., Thorley, A.J., Tetley, T.D., Forbes, B. Inflammatory response and barrier properties of a new alveolar type 1-like cell line (TT1) (2009) Pharm. Res., 26 (5), 1172-1180.

Publications: Polymeric nanoparticles for drug delivery

(38) Kakde, D., Powell, L.G., Bansal, K.K., Howdle, S., Irvine, D., Mantovani, G., Millar, G., Dailey, L.A., Stone, V., Johnston, H.J., Alexander, C. Synthesis, characterization and evaluation of in vitro toxicity in hepatocytes of linear polyesters with varied aromatic and aliphatic co-monomers (2016) J Control. Rel., 244, 214-228.

(39) Ahmad Khanbeigi, R., Kumar, A., Sadouki, F., Lorenz, C., Forbes, B., Dailey, L.A.*, Collins, H. The delivered dose: Applying particokinetics to in vitro investigations of nanoparticle internalization by macrophages (2012) J. Control. Rel., 162 (2), 259-266.

(40) Simon, M., Behrens, I., Dailey, L.A., Wittmar, M., Kissel, T. Nanosized insulin-complexes based on biodegradable amine-modified graft polyesters poly[vinyl-3-(diethylamino)-propylcarbamate-co-(vinyl acetate)-co-(vinyl alcohol)]-graft-poly(l-lactic acid): Protection against enzymatic degradation, interaction with Caco-2 cell monolayers, peptide transport and cytotoxicity (2007) Eur. J. Pharm. Biopharm., 66 (2), 165-172.

(41) Dailey, L.A., Kissel, T. New poly(lactic-co-glycolic acid) derivatives: Modular polymers with tailored properties (2005) Drug Discovery Today: Technologies, 2 (1), 7-13.

(42) Dailey, L.A., Wittmar, M., Kissel, T. The role of branched polyesters and their modifications in the development of modern drug delivery vehicles (2005) J. Control. Rel., 101, 137-149.

Publications: Nitric oxide

(43) Heikal, L., Starr, A., Hussein, D., Prieto-Lloret, J., Aaronson, P., Dailey, L.A., Nandi, M,*. L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex (2018) JACC Basic Transl Sci. (accepted Feb 2018)

(44) Heikal, L., Starr, A., Martin, G.P., Nandi, M., Dailey, L.A.* In vivo pharmacological activity and biodistribution of S-nitrosophytochelatins after intravenous and intranasal administration in mice (2016) Nitric Oxide, 59, 1-9.

(45) Heikal, L., Aaronson, P.I., Ferro, A., Nandi, M., Martin, G.P., Dailey, L.A.* S-nitrosophytochelatins: Investigation of the bioactivity of an oligopeptide nitric oxide delivery system (2011) Biomacromol., 12 (6), 2103-2113.

(46) Heikal, L., Martin, G.P., Dailey, L.A.* Characterisation of the decomposition behaviour of S-nitrosoglutathione and a new class of analogues: S-Nitrosophytochelatins (2009) Nitric Oxide, 20 (3), 157-165.

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