It is estimated that over 95% of the new drug candidates suffer from poor pharmaco-kinetic/ADME-properties when delivered orally. The main reasons for the inadequate oral bioavailability are poor thermodynamic solubility and/or dissolution rate of the compound in the intestinal lumen, inadequate permeability properties of the drug across the gastrointestinal (GI) wall, as well as high intestinal or hepatic first pass metabolism. Thus, due to the these problems in drug discovery, delivery systems addressing issues regarding low solubility and means to modulate drug permeability have been emphasized as key methodologies.
Peptides binding to tumor vessel expressing markers have shown to be highly specific to certain brain cancers. These peptides provide a possibility to produce therapeutic anti-tumor agents with minor side-effects. On the other hand, essentially 100% of large-molecule drugs and >98% of small-molecule drugs do not cross the blood-brain-barrier (BBB). This is the most important single factor limiting the development of new drugs for the central nervous system (CNS). For example, the targeting of early stage of brain cancers may be inefficient due to the intact BBB and thus, brain tumors (e.g. glioblastomas) are mostly inaccessible to traditional chemotherapy. Nanotechnology-based systems have shown to be efficient in crossing the BBB due to the appropriate chemico-physical characteristics of the surface of the nanoparticles, and they might be used to significantly improve the effect of brain cancer therapy.
Regarding the two above-mentioned examples mesoporous materials has been reported to promising and potential materials to overcome the problems encountered in development of effective drug delivery systems. Beside the synthesized bottom-up mesoporous silica materials also electrochemically etched top-down mesoporous silicon (PSi) materials can be utilized. As silica materials also silicon materials are biocompatible and biodegradable, and they possess some very beneficial properties regarding drug delivery applications. The small size of the pores confines the space of a drug and engages the effects of surface interactions of the drug molecules and the pore wall. The size of the pores and the surface chemistry of the pore walls may be easily changed and controlled. Depending on the size and the surface chemistry of the pores, increased or sustained release of the loaded drug can be obtained. Drug loading from a solution at room temperature (or below) enables the use of PSi also with sensitive therapeutic compounds susceptible to degradation, like peptides and proteins. When aiming oral delivery microparticles are utilized, and when to develop systems to cross BBB nanoparticles are employed. The particles can be functionalized to prolong the circulation time when injected intravascularly and to facilitate the passive and active targeting by making them magnetic and by means of targeting peptides, respectively.
- Enhancement of bioavailability of poorly water soluble drug by utilizing mesoporous silicon microparticles as drug carriers
- Development of mesoporous silicon nanoparticles to increase therapeutic effect of peptides and to across blood-brain-barrier
- Functionalization of silicon surfaces
- Development of drug loading methods
- Physico-chemical characterization of the loaded mesoporous particles
- Through collaboration partners: delivery related experiments (in vitro and in vivo) with the particles
Post-doc researchers: 3
PhD Students: 6
Assisting personnel: 4
Number of per-review articles 2004 - 2007: 59
Doctoral Dissertations 2002 - 2007: 3
Several Finnish and international university partners
Several Finnish and international company partners
Dos. Jarno Salonen
Laboratory of Industrial Physics
Department of Physics
FI-20014 University of Turku, FINLAND