Log in   

Login to your account

Arto Urtti, Ph.D, Professor

Arto Urtti received his Ph.D. in Pharmacy in 1986 (University of Kuopio, Finland). Professor Urtti has led the CDR at the University of Helsinki since 2005. Professor Urtti has authored more than 220 peer-reviewed articles and 20 patents and patent applications. Arto Urtti has received numerous scientific awards including: Innovation Award, American Association of Pharmaceutical Scientists Fellowship, Honorary Membership of the Finnish Pharmacists’ Association, the Albert Wuokko Prize, and the Millennium Distinction Award. He has served as editor-in-chief of the European Journal of Pharmaceutical Sciences and as editorial board member for many other international journals. Professor Urtti’s main research fields include drug delivery (controlled release, computational and cell-based methods for ADME research) and nanotechnology (biomaterial structures for drug and gene targeting and for 3-d cell cultures).
Tuesday, 25 June 2013 13:01

Transdermal Drug Delivery

Transdermal drug delivery is an optional mode of drug administration. It is a viable alternative if drug permeation across the skin is adequate. Formulation technologies can help in transdermal drug absorption, but skin irritation can often limit the use of these approaches. Appropriate cell culture models of the skin can help us to understand and predict these interactions; and, to facilitate development of new drugs as well as new drug formulations. In this regard, we have developed a human epidermis organotypic cell culture model that can be used for the analysis of transdermal drug delivery, high-throughput screening of chemical libraries, and development and testing of novel transdermal drug formulations.

Selected Publications:

All Publications

Professor Arto Urtti, Director of the CDR, also directs a research-oriented program for M.Sc. students in the Faculty of Pharmacy. This M.Sc. program offers an opportunity for talented and motivated students to conduct advanced course work and to develop hands-on scientific skills early in their training, paving the way for continuing Ph.D. studies or for industrial research and development positions upon graduation. Among current Master's students, prospective students are selected via grades, performance on university entrance examination, and subjective criteria to complete the program in Finnish. Selection takes place during the spring semester of studies based on separate application and interviews. The Finnish degree requirements for a B.Sc. (Farmaseutti) and M.Sc. (Proviisori) in Pharmacy will be met.
The research-oriented M.Sc. program in Pharmacy program also includes rotations (minimum 2 months per year) in laboratories. Here, students engage in hands-on research work as a member of an established research group. To ensure that selected students are allowed to fully concentrate on their research work as a full member of a selected research team, students will receive a salary.
For more detailed information, see here. For questions about the research-oriented program in Pharmacy, please contact the This email address is being protected from spambots. You need JavaScript enabled to view it..

Cellular and computational models are developed for improved prediction of clinical ADME properties. We are using and further developing the following epithelial cell models: Caco-2, MDCK, MDCK cell lines with transfected human transporter genes, blood-retinal barrier models, corneal and epidermal models. Furthermore, we have generated numerous Sf9 cells that stably express various human ABS efflux transporters. These cell models can be used for drug permeability and transporter interaction studies. Computational modeling activities can be divided into two categories: structure-based models and pharmacokinetic models. Structure-based models include QSAR for oral drug absorption. QSAR models for efflux transport and volume of drug distribution are being developed and tested continuously. Both in vitro and in silico data are integrated into pharmacokinetic simulation models that can be used to estimate the importance of different factors in the physiological setting.

All Publications

Monday, 20 August 2012 01:45

Complex Organotypic Cell Models

We have developed and investigated 3D cell cultures using: hepatocyte cell lines HepG2, HEPA-RG cells, and human embryonic stem cells. We observed stem cell differentiation toward hepatic progenitors and hepatocytes, but despite positive biomarkers (like albumin), these cells are not yet truly hepatocytes. For example, metabolic enzyme expression is low. In the case of HepG2 and HEPA-RG, we observed a polarized cellular phenotype within cellular spheroids cultured in peptide- and polymer-based nanofiber materials (1, 2). Importantly, we have also generated rigorous methods for 3D imaging of cell spheroids in biomaterials.

Microencapsulated cells may ultimately enable even permanent protein drug therapy with a single administration. Retinal pigment epithelial cell lines (ARPE-19) were cloned to secrete marker protein as well as soluble VEGF-receptor that acts by sequestering free VEGF from tissues. The net effect is to block VEGF activity. We microencapsulated these cells and demonstrated prolonged protein secretion from them (3, 4). This cell therapy research resulted in development and production of a laboratory scale cell microencapsulation device (4) as well as a demonstration of proof-of-principle that cell viability could be preserved in microcapsules during freeze-drying (5). Such methods could facilitate the future logistics for use of polymer-embedded cell therapy products.

Selected Publications:

1. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. M Bhattacharya, M Malinen, P Lauren, YR Lou, C Parras-Cicuendez , S Kuisma, L Kanninen, M Lille, A Corlu, C Guillozo, A Laukkanen, A Urtti, M Yliperttula.  J Control Release, in press.

2. Peptide nanofiber hydrogel induces formation of bile canalicular structures in 3D cultures of hepatic cell line. M. Malinen, H. Palokangas, M. Yliperttula, A. Urtti.  Tissue Engineering Part A, in press.

3. Kinetic simulation model of protein secretion and accumulation in the cell microcapsules. Wikström J, Syväjärvi H, Urtti A, Yliperttula M. J Gene Med 10: 575-582, 2008.

4. A laboratory scale device for straightforward production of small uniform sized cell microcapsules with long-term cell viability. L. Kontturi, M. Yliperttula, P. Toivainen, A. Määttä, A.M. Määttä, A. Urtti. J Control Rel 152: 136-141, 2011.

5. Viability of human retinal pigment epithelial cells. J. Wikström, M. Elomaa, L., Nevala, J. Räikkönen, A. Urtti, M. Yliperttula. Eur J Pharm Sci 47: 520-526, 2012.

All Publications

Monday, 20 August 2012 01:29

Nanocarriers and Drug Delivery

Biomaterials are useful in drug delivery and targeting, since they can be optimized as controlled release formulations and also as nanoparticles for intracellular drug delivery. Our unique interdisciplinary research program couples both physico-chemical and biological aspects in this area. The research is focused in particular on continuous protein delivery from microencapsulated cells and on nanoparticle-mediated gene delivery and targeted anti-cancer drug research.

Our group performs mechanistic research with nanoparticulate systems with the aim of better understanding the delivery process. Packing of pDNA with polycations is used to form DNA nanoparticles, but structural features of the resulting nanoparticulates are poorly understood. A new time-resolved spectroscopic method was established for DNA packing studies (3,4). The method revealed interesting differences between PLL- and PEI-DNA complexes; the latter shows tightly bound and mobile DNA, whereas PLL-DNA complexes have only tightly bound DNA. The mobile PEI-based complexes have about 100-fold higher activity of transfection per DNA copy delivered to the cell nucleus. We have also demonstrated that the interactions of free PEI with cell surface glycosaminoglycans (GAG) improve DNA transfection, presumably by a decoy effect that reduces the interactions between the complexes and GAGs (5). We also performed a careful mechanistic study to investigate cell penetrating peptides that have been claimed to permeate directly through the cell membrane. In contrast to published reports, we did not observe this. All TAT-peptide variants were endocytosed and trapped within endosomal and lysosomal vesicles (8). 
Our group has also investigated different nanocarriers as new drug delivery systems. For gene delivery, we investigated DNA complexes that were coated with hyaluronic acid (mw 10 kDa). This coating provided gene delivery via CD44-receptor mediated endocytosis (8). Two other receptor mediated drug-targeting systems were investigated: liposomes decorated with EGFR targeted antibodies or neovascularization targeted peptides (1,3). We investigated both systems using various cellular methods, SPECT/CT imaging, mass spectrometric drug distribution analyses, and molecular dynamics simulations. Some targeting efficiency was seen with the antibodies, but the peptide targeting failed. This could be explained using molecular dynamics simulations of the liposomal surface, which suggested that the PEG chains of the liposome shielded the hydrophobic peptide on the liposomal surface. 
Light triggered drug release from liposomes has been achieved by incorporating gold nanoparticles into liposomes (6,7). The gold nanoparticles absorb light, and the energy is transferred as heat to the lipid bilayer that becomes more leaky and releases the drug. High-resolution SAXS measurements reveal that the light induces phase changes in the gold embedded liposomes similar to the changes that are induced by temperature. This suggests that this action is mediated by heat release from the gold nanoparticles. Our data demonstrated drug release from liposomes within the cells, but we did not alter the probe distribution in the cells (i.e., it was retained within endosomal and lysosomal vesicles). 

Selected Publications:


Monday, 20 August 2012 01:10

Ocular Drug Delivery and ADME

Ocular drug delivery is a limiting factor in the development of new medications to the treat diseases of the posterior eye segment. Research on delivery systems, test models and computational models opens avenues for improved ocular drug treatments. Our group has more than 20 years of experience in ocular drug delivery including: cell model development, drug discovery, drug formulation, kinetic modeling, and basic cell research of the eye. The research group is multidisciplinary including expertise in pharmaceutical sciences, molecular and cell biology, materials science, bio-organic chemistry, physical chemistry, and molecular modeling.

Retinal pigment epithelium (RPE) is the main component of the blood-retina barrier that regulates the access of drugs from blood circulation into the eye and vice versa. Currently, there is no established cell model for this important PK barrier. We established an immortalized human cell model of RPE (1). This model shows fairly close values of epithelial permeability for a range of drugs and macromolecular probes. However, this model is also an immortalized cell line that may deviate from the normal RPE cells in human eye. For example, normal cells contain melanin granules and are highly pigmented. Therefore, we extended our research to human embryonic stem cells. In this model, cells are cultured and differentiated on porous polyimide membranes that are coated with extracellular matrices. We discovered ECM coatings and culture conditions that supported differentiation into a stem cell-derived RPE mimic (2). These cells are highly pigmented, they express many RPE-specific markers, they display proper barrier properties, and they phagocytose rod outer segments (the normal function of the RPE). This is a promising result that paves the way to realistic blood-retina barrier cell models and to RPE transplantations on biomaterial supports. The latter is a potential treatment in age-related macular degeneration.


We characterized an immortalized human corneal epithelium cell model (HCE) for ocular absorption studies. The physical barrier properties and the relevance of this cell model were established earlier. However, the efflux transporters and monocarboxylic acid transporters in the model showed different expression profiles  compared to human corneal epithelium (3, 4). Universal expression analysis with DNA arrays (aaproximately 11,000 genes) was performed on HCE cell model and human corneal epithelium (5). The expression profiles were strikingly different demonstrating the power of systems biology approaches in the evaluation of ADME cell models and the limitations of the HCE model.


We have generated a series of baculovirus-infected insect cells for selective over-expression of efflux proteins MRP-2, MRP-4, MDR-1, and BCRP. The systems are used to investigate the efflux protein interactions of chemical libraries. The goal is to make QSPR models of these interactions. We performed experiments with MRP-2 overexpressing cells, and the modeling is under way. We have also demonstrated that various assays yield different conclusions on drug interactions with MRP-2 (6). Furthermore, we showed that the corneal epithelium and RPE (anterior and posterior ocular barriers) express MRP-1, MRP-4 and MRP-5 (3, 7). This profile is different from many other barriers. The PK importance of these transporters in the eye remains to be discovered.


Ocular ADME modeling is an important tool in understanding the relationships between molecular structure and PK properties in the eye. Along these lines, we have carried out modeling of all existing and curated data on corneal drug permeability (describes ocular absorption) and half-life in vitreous (describes elimination and distribution in the posterior eye segment). In both cases, we were able to generate a reliable model with only two chemical descriptors (8, 9). These models are useful tools in estimating the PK behavior of ocular compounds early in drug discovery.


Sub-conjunctival administration is an interesting alternative to more invasive intravitreal ocular injections, but yet this route is poorly understood. We built the first PK simulation model that includes all relevant parameters (elimination from subconjunctival site to blood and lymphatic flow, scleral permeability, choroidal elimination to blood flow, RPE permeability and vitreal elimination). The simulations show that, eventually, high molecular weight is beneficial for drug delivery. Large molecules are lost to blood flow slower than small compounds, and this factor is more important than the permeability advantage of small molecules (10). The model also provides insights on strategies for posterior segment drug delivery.

Selected Publications:

9. Kidron H, Del Amo E, Vellonen K.S., Urtti A: Prediction of the vitreal half-life of drug-like compounds. Pharm Res, in press

All Publications


Monday, 20 August 2012 00:53

Drug Delivery and Nanotechnology

Drug delivery is an essential part of pharmaceutical sciences that should be taken into account early in the drug discovery and development process. A drug that cannot be delivered to its site of action is essentially useless. Drug delivery is affected by the physico-chemical properties of the drug and formulation and the interplay of these factors with the transport, binding, and metabolism of the drug in the body. New tools are needed to accurately predict delivery properties of the compounds early during drug discovery, so that the best compounds can be identified for clinical studies. Another class of tools includes the delivery methods that facilitate delivery of hard-to-deliver compounds to the appropriate target sites. Delivery of gene-based drugs (DNA, oligonucleotides, siRNA) and proteins is a major challenge in pharmaceutical science. Nanotechnology can be used to improve drug delivery in these difficult cases. The development and use of nanoparticles in the formulation of these types of drugs is a major focus at CDR, and we welcome productive industrial partnerships to develop these tools for translational use.

Ocular Drug Delivery and ADME — Treatment of retinal diseases (e.g., age-related macular degeneration, glaucoma, diabetic retinopathy) is hampered by ineffective and/or short-acting drug delivery to the target cells. Eye drop instillation results in negligible (0.001%) bioavailability in the retina. Intravitreal injections deliver drug to the retina, but this is rarely feasible, because vitreal half-lives of most drugs are below 10 hours. Periocular (sub-tenon, subconjunctival), subretinal and suprachoroidal routes of drug administration are potentially useful, but again, efficacy and/or duration of action are not adequate. Minimally invasive, long acting, and effective drug delivery would be a major breakthrough in ophthalmic drug treatment. Development of improved delivery systems requires proper understanding of ocular pharmacokinetics and construction of the delivery systems. Surprisingly, the expression and activity of drug transporters in the eye is poorly understood. Further, the QSPR of drugs’ ADME properties in the eye have only rarely been explored. New and improved delivery systems should provide prolonged drug action (i.e., ocular injection 1-2x per year) and effective dosing of otherwise inactive drugs. We are investigating ocular ADME and drug delivery issues in our research program.

Nanocarriers for Drug Delivery — Nanocarriers are widely investigated as potential solution for delivering drugs and genes into target sites. Important issues in this research include physical-chemical assembly of the nanocarriers, their surface interactions with biological media, cellular interactions, and controlled content release from the carriers. These issues must be understood, otherwise, the delivery process may be unreliable and only poorly effective. In our research program, we investigate DNA delivery by using nanoparticles – a complex and poorly effective process that is not well understood. We also carry out research on liposomes in relation to drug targeting and to light-triggered drug release.

Complex Organotypic Cell Models — Recent developments in biology (including stem cell biology, cell cloning, and induced pluripotent stem cells), and materials science (including responsive materials and nanofibers) have set the stage for improved 3D and other organotypic cell models that more accurately mimic human tissues. Biomaterial-based cell culture technologies are highly valuable as in vitro drug development tools and as potential cell therapies. We are currently investigating blood-retina barrier cell models, 3D cultures of hepatocytes and epidermis, and cell therapy approaches (e.g., cell microencapsulation).


From the Director

You must have the Adobe Flash Player installed to view this player.

Recent Activities