PhD Scientific Days 2023

Pharmaceutical Sciences - Posters F

Paving the Path for Disulfiram Anticancer Repositioning

Előadó neve

Dr. Benkő, Beáta Mária

Neptun code

PRCN09

Előadó munkahelye

University Pharmacy Department of Pharmacy Administration, Semmelweis University

Előadó telefonszáma

0036309527963

Előadó e-mail címe

benko.beata@phd.semmelweis.hu

Az előadás címe

Paving the Path for Disulfiram Anticancer Repositioning

Szerző(k) neve és munkahelye

Beáta Mária Benkő1, Gergő Tóth2, Zoltán István Szabó3, Lajos Szente4, Bence Tóth5, Romána Zelkó1, István Sebe1
1 University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary
2 Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
3 Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, Romania
4 Cyclolab Ltd., Budapest, Hungary
5 Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences - Posters F

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction:
Since disulfiram’s (DS) approval as an anti-alcoholism drug, extensive investigations have been carried out to explore other biomedical and pharmacological effects. In the past two decades, comprehensive anticancer mechanisms of action of DS were proposed and many molecular biological targets were identified, but the preliminary data from clinical trials show unsatisfactory results, not supporting the promising preclinical data. The deviation could be attributed to the drug`s poor solubility, instability, low bioavailability, rapid, unwanted metabolism, and poor delivery efficiency to tumor tissue, suggesting that the repositioning needs to be reached from both clinical and technological perspectives.
Aim:
The aim is to pave the path of DS anticancer repositioning with pharmaceutical technology tools by encapsulating the drug in cyclodextrin (CD) inclusion complexes to increase the solubility and stability, and promote the development of non-invasively administrable pharmaceutical forms.
Methods:
For the solubility and stability enhancement of the BCSII class drug (Sigma Aldrich), CD inclusion complexes were studied. Native (α-, β-, γ-CD) and pharmaceutical grade CD derivatives [hydroxypropyl (HP-β-CD), randomly methylated (RM-β-CD) and sulfobutylether sodium salt (SBE-β-CD)] (CycloLab) were selected. Solubility study and solid-state characterization of the inclusion complexes were assessed to determine the suitable formulation.
Results:
DS could play an adjuvant role in cancer therapy, enhancing the standard management protocol by radiotherapy and chemo-sensitizing effect and suppressing the tumor mass, thus inhibiting the cancer progression. The clinical translation of this adjuvant drug into cancer therapy can only be achieved with optimized drug delivery systems that overcome the poor bioavailability and low tumor-mass targeting efficacy. The solubility of DS was significantly increased by the CD derivates, and inclusion complex formation was achieved with CD derivatives, serving for a value-added pharmaceutical formulation of repurposed DS.
Conclusions:
The technological development strategy to encapsulate DS via CDs and to develop parenteral formulations with favorable pharmacokinetic profiles shows promise for the effective application of DS, ensuring drug solubility, stability, and accurate delivery into the tumors.
Funding: STIA-KFI-2022

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Sebe István

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7451

Start

11:06

End

11:11

Authors (legacy)

Beáta Mária Benkő1, Gergő Tóth2, Zoltán István Szabó3, Lajos Szente4, Bence Tóth5, Romána Zelkó1, István Sebe1
1 University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary
2 Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary
3 Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, Romania
4 Cyclolab Ltd., Budapest, Hungary
5 Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary