In MOIN we do drug delivery system development using imaging as a tool. We have our own theranostic nanoparticles and we do custom drug delivery solutions to our partners. There are several possible payloads including proteins peptides DNA, RNA small molecules etc that can be targeted to the disease site by using our liposomal nanotechnology. We do labeling of the target molecules as well and have several possibilities for labeling.

Theranostic strategy means combination of therapy and diagnostics. This approach tries to combine the strengths of the rapid late development of the imaging technologies and the possibilities that nanotechnology offer. Liposomes are very well suited to theranostic approaches because liposomes can carry simultaneously several cargoes like two imaging modalities and a drug. Because the different limitations of each imaging modality it makes sense many times to have more than one imaging probe like PET probe for quantification of the liposomes and a MRI probe for morphological imaging. In future this kind of probes will be more popular when MRI/Optical Optical/CT MRI/PET, MRI/SPECT, PET;CT MPI/CT and SPECT/CT combinatorial imaging equipment will be more common. At the moment this kind of multimodal imaging can be performed with MOIN equipment. The output for these probes can be easily integrated with more advanced delivery systems, like thermo-sensitive liposomes, where medical care personnel can release the drug when simultaneously observing the delivery vehicles to be in the same location as the site of illness. This will probably be even more important when gene therapy will be more common while liposomes are already extremely efficient transfection facilitators.

The nanoparticles allow versatile platforms that can be used for multifunctional drug delivery systems. There are MRI imaging technologies that can locate tumours of only several millimetres in size and there are targeted delivery systems that can deliver drugs to the site of the tumour more efficiently than the free drug and which can be used for imaging. However there is not jet a system that can combine all of these systems and give a treatment option where you can image the tumour and wipe out the imaged tumours non- invasively. Delivery technologies and nanotechnologies together with biotechnology-derived drugs will bridge the gap in the future.Nanotechnology will be used more as part of main stream drug development and drug delivery. The knowledge of the use of nanotechnology is increasing.

Liposomes are self-assembled vesicles composed of a lipid bilayer, which forms a closed shell surrounding an internal aqueous phase. The size, charge, components, and molecular modifications of liposomes are easily controlled. One of the advantages of liposomes as drug carriers is that they can carry both hydrophilic and hydrophobic molecules. On the other hand liposomes have a surface that can be used for attachment of various targeting ligands and reporters.

Liposomes and micelles are common nanostructures in clinical use for drug delivery. By preferentially enhancing localization of pharmaceutical activity in the organ/tissue of interest, their use has the potential to reduce the required systemic dose of drugs, thus minimizing risks of adverse side effects while increasing treatment efficacy. Liposomes have been generated in several institutions and companies in multiple settings and in different formulations in GMP conditions for clinical use and they are generally well tolerated.

Imaging studies can help to assess biodistribution as well as pharmacokinetic and pharmacodynamics (PK/PD) parameters of nanodelivery systems in preclinical testing and in humans, and facilitate clinical development in phase I / II trials without risking the patient.

Thermosensitive liposomes (TSL) are drug delivery systems that allow controlled release of their payloads resulting from regional hyperthermia (RTH) . In this process, lipids change from a gel to a liquid state at a species-specific temperature, called a transition temperature (Tm). Every lipid molecule in the liquid phase requires more space than in the solid phase due to the additional freedom of the lipid molecules in the membrane.

Magnetic liposomes allow a platform that is flexible and versatile enough to allow variations from patient to patient. This together with the imaging techniques MRI and MPI allows in to diagnose the patients in the level that is just approaching to our consciousness and to treat them in a way where the effectiveness of the treatment is monitored close to real time. Theranostic approach will also make microdosing studies possible. In microdosing imaging is used to evaluate PK parameters before phase one and two. Microdosing study before phase II studies would allow researchers to see if the cure reaches to the site of the disease and if there is favorable response in molecular level. However, it should be remembered that a change of paradigm in the treatment can take several decades rather than months or years but in the end nanotechnology combined with imaging techniques, based on the evidence shown so far, will revolutionize the medicine.

Nanocarriers can aid in the physical, chemical, and physiological stability or solubility of the encapsulated therapeutic entity. In addition, they are able to modulate these entities in organ, tissue, cellular, and sub-cellular transport. In terms of pharmaceutical applications, this could lead to better targeting and/or lower side effects. Therefore, there is a strong need to develop in vivo nanoprobes for drug targeting, functional imaging, and targeted therapy.

There are several prerequisites for clinical translation of a nano-delivery system, and therefore some nanoparticles are more suitable than others. As all parenteral delivered substances, sterility and non-toxicity are mandatory. Additionally, there is consensus that the nanocarriers have to be biodegradable, in the same fashion as liposomes, micelles and other lipid-derived nanoparticles. Alternatively, they have to be cleared from the body quickly, predominantly through the kidney.

Although useful for passive accumulation of drugs or imaging agents in tumors or areas of inflammation and cancer, the EPR effect increases the non-specific background significantly for any specific approach. Elaborate controls are needed to distinguish between effects caused by specific targeting or by EPR. There is data available demonstrating that the amount of EPR effect depends mainly on the physicochemical characteristics of the macromolecules/nanoparticles and less on the tumor morphology and vascularization. However, more data is needed to fully understand the underlying mechanisms, and potentially use the EPR effect in a more sophisticated way for drug delivery to tumors and areas with inflammatory activity. Until then, any macromolecular or nanoparticle system using site-specific targeting or activation needs to accurately control for non-specific accumulation of the vehicles via EPR effect.

An integral feature of targeted therapy is the release of the therapeutic moieties at the site of interest. This can be achieved by incorporation and digestion of the nanocarriers by the diseased cells, by enzymatic activation of a pro-drug conjugated to the carrier surface, or by diffusion of the drug out of the carrier matrix. However, balance of safe encapsulation during systemic passage and sufficient release at the site of action is not trivial. This issue can be addressed by conjugating the active moieties to the surface, but it has to be proven that the drug is still active after the conjugation procedure, that it is not cleaved off in the circulation, and that the adverse side effects caused by ectopic activity are tolerable. Nanodelivery systems that are activated at the site of action by disease-specific reactions would be favorable.

For the application of nanoparticles in DDS, evaluation of nanoparticles fate in vivo is important. Biodistribution has usually been evaluated invasively in sacrificed animals after injection of radiolabeled nanoparticles. Imaging enables non-invasive determination of nanoparticles fate.


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