PhD Scientific Days 2020

Pharmaceutical Sciences II. Posters

Novel Cyclodextrin-based Drug Carriers to Target the Blood-brain Barrier: Synthesis, Analytical- and In Vitro Characterisation

Előadó neve

Kalydi, Eszter, MSc

Előadó munkahelye

Department of Pharmacognosy, Semmelweis University, Budapest

Előadó telefonszáma

+36705256161

Előadó e-mail címe

kalydie@gmail.com

Az előadás címe

Novel Cyclodextrin-based Drug Carriers to Target the Blood-brain Barrier: Synthesis, Analytical- and In Vitro Characterisation

Szerző(k) neve és munkahelye

Eszter Kalydi1,2, Milo Malanga2, Mihály Bálint2, Erzsébet Varga2, Szabolcs Béni1, Gábor Benkovics2
1Department of Pharmacognosy, Semmelweis University, Budapest
2CycloLab, Cyclodextrin R&D Ltd, Budapest

Szekció

Pharmaceutical Sciences II. Posters

Language of the presentation

English

Section, first choice

Pharmaceutical Sciences

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction
In the development of new drugs for neurological diseases, the main limiting factor is the presence of the blood-brain barrier (BBB), inhibiting the delivery of therapeutics into the brain. Glucose transporters provide ideal targets for new carrier systems aiming the central nervous system (CNS), as they are overexpressed on the surface of the BBB.1 Another approach is the use of positively charged carriers to achieve high affinity for the negatively charged endothelial cells of the brain capillaries. It is evidenced, that organizing monomeric compounds to macromolecular systems enhances their transport across the cell membranes.2

Aims
As cyclodextrins (CDs) are known as ideal drug carriers, our aim was to develop new CD-based drug delivery systems, capable to cross the BBB. Based on the aforementioned considerations, we have synthetized two sets of CD derivatives: (1) glucose appended beta-CD (BCD) and hydroxypropyl-BCD (HPBCD) scaffolds using click-chemistry, (2) positively charged polymer by crosslinking (2-hydroxy-3-N,N,N-trimethylamino)propyl-BCD (QA-BCD) with epichlorohydrin.

Method
For the in vitro investigation of the compounds, their fluorescent labeling was necessary. As fluorescent tags, 7-alkylamino-4-nitrobenzofurazan (NBF) and fluorescein-isothiocyanate (FITC) were used. The labelled glucose-modified CDs were synthetized by the simultaneous attachment of the fluorophore and a targeting unit via click-reaction and characterized by NMR and MALDI-TOF-MS. The FITC-labelled polymers were synthetized through a copolymerization of the QA-BCD and 1% FITC-BCD monomer and characterized using NMR and dynamic and static light scattering.

Results
Cellular internalization properties of the conjugates are under investigation using isolated human brain microvascular endothelial cells (HBEC-5i). The HBEC-5i monolayer serves as a barrier model. Confocal fluorescence microscopy is used to determine the internalization process and flow-cytometry is used to quantify the cell-penetration.

Conclusion
Various new CD-based drug carriers targeting the CNS have been synthetized and characterized by NMR, MS and microscopy.

The authors kindly appreciate the financial support for Gedeon Richter Ltd and the ÚNKP-19-4-SE-53 fellowship.

1Machut-Binkowski et al, J. Incl. Phenom. Macrocycl. Chem., 2007; 57: 567-572
2Pandey et al., Tissue Barriers, 2016; 4:1

Additional Information

Supervisor: Szabolcs Béni
E-mail address: beni.szabolcs@pharma.semmelweis-univ.hu

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4785

Start

12:58

End

13:01

Authors (legacy)

Eszter Kalydi1,2, Milo Malanga2, Mihály Bálint2, Erzsébet Varga2, Szabolcs Béni1, Gábor Benkovics2
1Department of Pharmacognosy, Semmelweis University, Budapest
2CycloLab, Cyclodextrin R&D Ltd, Budapest