Molood Shariati

Molood

 

Contact

Laboratory for General Biochemistry and Physical Pharmacy
Ghent University
Ottergemsesteenweg 460
9000 Gent
Belgium
Tel: 0032 9 264 80 47 (secretary)
Tel: 0032 9 264 83 65 (direct)
Fax: 0032 9 2648189
E-mail:

Biography

Education:

2010-2013
Master’s degree student in Cellular and Molecular Biology-Genetics at Tarbiat Modares University. Tehran, Iran
(Master thesis entitled : Investigation of Dendrosomal Curcumin inhibitory effect on the Human Telomerase Reverse Transcriptase gene ( hTERT ) promoter through induction of TGFβ1 signaling pathway in hepatocarcinoma cell line (Huh7) )

Research interests:

Nanomedicine, nanoparticle-based drug delivery systems, Anti-cancer Agents, Chemotherapeutics 

Summary of Research Project(s)

The IP perfusion of small molecule anticancer drugs is already used in the post-surgical treatment of PC, but they typically rapidly leak from the peritoneal cavity to the systemic circulation. Nanoparticle (NP) formulations could increase the local retention of anticancer drugs in the peritoneum. To date, most NP formulations were developed for IV injection. To design an NP for PC, some special constraints should be kept in mind. Most importantly, the rate of degradation of the NP should meet the controlled delivery requirements for a given anticancer drug. Also, the clearance of NP from the peritoneum should be minimal, to prevent redistribution to the systemic circulation. Therefore, it is clear that knowledge on the biodistribution and stability of NP in the peritoneal fluid is crucial to allow for optimization of the NP delivery systems. So far, however, NP behavior in the peritoneal cavity has not been investigated in detail, partly because of a lack of suitable methods to perform measurements directly in the IP fluid.
Our laboratory develops and optimizes the use of advanced microscopy techniques such as Fluorescence Fluctuation Spectroscopy (FFS) and Single Particle Tracking (SPT) to study nanoparticle behavior in complex extracellular matrices. These in-house developed methods allow to quantitatively measure the concentration of NP in blood and IP fluid. In addition, the encapsulation efficiency and stability of NP can be directly measured in the peritoneal fluids. Finally, SPT monitors the size of the NP at all times. This is an important feature, as NP can aggregate in the IP fluid to form agglomerates from up to 10-20 times more than their original size. As several NP features such as the release of chemotherapeutics, the clearance from the IP cavity and the penetration depth into the tumor nodules are expected to be size dependent, monitoring the actual size of NP during delivery is crucial, ensuring the behavior of NP is attributed to its actual size. In this work package, we aim to perform an in-depth study on the physicochemical properties that are optimal to deliver anticancer drugs in the peritoneal cavity by using NP, for a prolonged period of time. Different subtasks are:
-    Determine encapsulation efficiency of CIS, OXA and PTX in NP formulations by FFS
-    Follow the release of anticancer drugs from selected formulations as a function of time in IP fluid by FFS
-    Determine size (between 20 nm – 2 µm) and charge (+, - and neutral) dependent aggregation and clearance of NP from the peritoneal cavity following IP administration by SPT
-    Tissue distribution and fluorescence imaging of NP in healthy and tumor bearing mice following IP administration

schema Molood

Fig.x  Overview of different important aspects determining the fate of NP in the IP cavity. NP efficiency will be determined by 1) release rate of CIS, OXA and PTX from the NP, 2) extent of NP aggregation in the IP fluid, 3) diffusion and uptake of NP into the tumor nodules and 4) the drainage of NP from the IP cavity to the blood circulation or lymphatic system. Ideally, NP should remain in the IP cavity during a prolonged period of time and target the metastatic cells.