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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).

 
 
 
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).

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