BrainMap

Mr. Lucian Bahrin

Dr.

Researcher - INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI"

Researcher

Curriculum Vitae (26/06/2023)

Expertise & keywords

Restore Her2 dependent sensibility using AXL inhibitors packed in pH dependent nanostructures Call name: EEA Grants - Proiecte Colaborative de Cercetare
EEA-RO-NO-2018-0246 2021 - 2024

Role in this project:

Coordinating institution: INSTITUTUL REGIONAL DE ONCOLOGIE IAŞI

Project partners: INSTITUTUL REGIONAL DE ONCOLOGIE IAŞI (RO); INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO); OSLO UNIVERSITETSSYKEHUS HF (NO)

Affiliation:

Project website: https://www.nanoher2restore.ro/

Abstract:

This project (NANOHER2RESTORE) proposes to apply modular supramolecular assembly consisting of pH sensitive units, recognition moieties and functional molecules to build up therapeutic entities sensitive to the tumour microenvironment and to investigate mechanisms for targeted breast cancer treatment in vitro and in vivo.

Our concept is based on the utilization of the specific extratumoral pH values as trigger for the targeted localized delivery by nano modular assemblies. The pH dependent self-assembly of the modules is ensured by the presence of block copolymers able to self-assemble into bilayers or vesicles. Furthermore, increasing the hydrophilic volume fraction favors the formation of structures with greater interfacial curvature, such as cylindrical or spherical micelles. These nano/micro structures can be used to encapsulate therapeutics (HER2 blockers and AXL inhibitor, doxorubicine, etc.), to protect the therapeutic agent (upon injection into the body) and to improve circulation times, thereby increasing the amount of active drug that reaches the targeted site. Specific coupling will be used for targeting molecules (trastuzumab) in order to protect Her antigen recognition site and use this recognition to enhance distribution in tumor site, based on over expression of Her on cellular membranes. Once the nano carrier reaches its target site, the drug is released by stimulus-triggered changes to the micelle, passive EPR effect on vesicle nanostructure to accomplish its therapeutic goal. We will use the modified acidic microenvironment of the tumor to produce a structural change in the co-polymeric blocks leading to disorganization of micelle type nanostructures, leading to drug deployment of the desired drug. Axl inhibitors are targeting the Her2 pozitive breast cancer cells in an effort to block an escape mechanism after long standing Her blockade.

The advantage of this delivery method is that we target tumor tissue using pH variations in the microenvironment and concentrate in the same area a dual approach of the tumor cells with both Her2 antibodies (trastuzumab) which remains active on the copolymer branch, as well as an AXL inhibitor. Delievered in the same are they aim to reactivate the Her2 blockade efficacy and render breast cancer cells sensitive to trastuzumab.

[2.2]Paracyclophane linkers for Metal-Organic Frameworks Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-0751 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI"

Project partners: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Affiliation: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Project website: https://icmpp.ro/projects/l1/about.php?id=20

Abstract:

Metal-Organic Frameworks are crystalline porous materials consisting of metal nodes linked together my organic linkers. Although relatively new, MOFs have quickly become an intensely studied field due to the potential applications in fields such as energy, catalysis or sensor design.

This project aims to obtain several new organic linkers based on a [2.2]paracyclophane core, which will then be used in the synthesis of [2.2]paracyclophane-based MOFs. The desired linkers will vary in shape (linear vs. angled), length and number of functional groups (ditopic vs. tetratopic). The metals that will be used in this project will come from both the s block (alkaline and earth metals), as well as the d block (3d and 4d metals). Once synthesized, the MOFs will be characterized and their sorption properties will be evaluated using nitrogen as an adsorbate.

The idea to use [2.2]paracyclophane derivatives in MOF design is a mostly unexplored avenue, therefore successful implementation of this project will deliver new and interesting structures with potential gas storage properties.

The synthesis and evaluation of some tribenzotriquinacene-flavonoids tripodal antibacterial agents Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2016-1117 2018 - 2020

Role in this project: Project coordinator

Coordinating institution: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI"

Project partners: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Affiliation: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Project website: http://icmpp.ro/seftaa/

Abstract:

Since their discovery, the overuse of antibiotics in both medicine and agriculture has paved the way to the emergence of drug resistant bacteria, which in turn gave rise to an ever-increasing demand for new, more effective antibiotics. Many of the recently developed drugs, however, were built on the same molecular scaffolds as older antibiotics, that various bacteria have developed resistance to. For instance, the second, third and fourth generation cefalosporins were each developed as microorganisms became resistant to the previous generation. The development of antibiotics based on new molecular scaffolds, that are able to bypass the various resistance mechanisms employed by drug resistant bacteria, is becoming more urgent with each passing day.

Flavonoids are a diverse class of plant polyphenols that exhibit a wide range of biological activities. Amongst these, several flavonoids were found to display antibacterial properties. Moreover, flavonoids have also been shown to have a synergistic effect when administered with other antimicrobial agents against drug resistant bacteria. This makes flavonoids promising candidates in the ongoing search for new antibacterial drugs.

The project leader previously worked on a class of tricyclic flavonoids bearing a 1,3-dithiolium ring that displayed strong antimicrobial properties. By grafting these to a tribenzotriquinacene unit, this project aims to synthesize a new class of tripodal antibacterial agents. Once synthesized, these derivatives will be tested against various lines of bacteria, their structure will be optimized and preliminary cytotoxicity tests will be performed. Successful implementation of this project should deliver effective antimicrobial agents based on a new molecular scaffold, with the potential of limiting the loss of human lives and reducing treatment time and costs.

1,3-Dithiolium Flavonoids With Antimicrobial Activities Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-1817 2017 - 2018

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.chem.uaic.ro/files/File/2017-2018/cercetare/proiect-prof-birsa/152-ped-birsa.pdf

Abstract:

The antibacterial properties of a new class of synthetic 1,3-dithiolium flavonoids is investigated in order to disclose new antibacterial drugs, disinfectants or antiseptics products. The objectives of this study are the following:

1. Optimization of 1,3-dithiolium flavonoids synthesis and evaluation of their structural stability. Synthetic optimization targets a one-pot synthesis and a large scale procedure, necessary steps in order to prepare a strategy for a technological transfer. Investigations of the tricyclic flavonoids stability in solutions or in solid state under various conditions will be performed before beginning the antimicrobial or cytotoxicity tests.

2. Preparation and morphology optimization of biocompatible polymeric membranes for controlled release of flavonoides potential drugs using transdermal patches. In order to achieve this objective we intend to use biocompatible polymers and prepare membranes loaded with the flavonoides suitable for controlled drug delivery.

3. To test the antimicrobial properties and understand the mechanism of action. The susceptibility of a wide range of bacteria to 1,3-dithiolium flavonoids will be assessed in relation with reference antibiotics; MIC/MBC values will be determined for future practical applications.

4. To investigated the cytotoxicity effects of the 1,3-dithiolium flavonoids. The output of this objective will guide us through an opinion about the potential use of these compounds as new antibacterial drugs/disinfectants/antiseptics.

5. Comparative analysis of the results for laboratory validation of the best candidate as antibacterial agent

6. Preparation of a patent applications

The study of the effect of organic complexing agents of Fe(III) or Fe(II) on iron monosulfide oxidative dissolution Call name: Joint Applied Research Projects - PCCA-2011 call, Type 1
PN-II-PT-PCCA-2011-3.1-0683 2012 - 2016

Role in this project:

Coordinating institution: UNIVERSITATEA DIN CRAIOVA

Project partners: UNIVERSITATEA DIN CRAIOVA (RO); UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA MATERIALELOR BUCURESTI RA (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.chem.uaic.ro/files/file/ecafe/index.html

Abstract:

The iron monosulfides (FeS) oxidative dissolution is a process that produces various environmental problems. Although the dissolved oxygen is the final acceptor of the electrons (and most common oxidant in natural environments), the actual species that takes electrons from mineral sulfides is ferric iron (Fe(III)). Accordingly, the control of Fe(III) concentration can suppress the oxidation of FeS. A study in quasi-environmental conditions, in the presence of Fe(III) or Fe(II) (ferrous iron, the species that generates Fe(III) in the presence of oxygen) complexing agents (ligands), can lead at a better understanding of FeS oxidative dissolution process, as well as at the proposal of adequate strategies for its suppression. Taking into account the importance and complexity of this subject, the study that will be realized is focused on two directions: a theoretical direction of fixing of the main aspects of FeS oxidative dissolution and, respectively, a practical direction, materialized by experimental studies, having as objectives achievement of our own results and their interpretation regarding to literature data. The main purposes of this study are the accurate characterization of FeS oxidative dissolution process in presence of Fe(III) and Fe(II) complexing agents, determining the temporal evolution of some indicators of FeS oxidation degree (pH, Eh, total iron concentration, total dissolved sulfur concentration, corrosion current densities, polarization resistances, etc.), surface analysis of reacted mineral samples by X-ray diffraction (XRD), FTIR spectroscopy, Raman spectroscopy, Atomic Force Microscopy, Scanning Electron Microscopy and the selection of ligands having an adequate inhibition efficiency of FeS oxidative dissolution, in order to create effective strategies of the suppression of the environmental contamination.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects