Poster Session III. - H: Pharmaceutical Sciences and Health Technologies
Dr. Benkő Beáta Mária
PRCN09
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary
+36309527963
benko.beata@phd.semmelweis.hu
Advancing Cancer Treatment through the Repositioned Disulfiram Drug Delivery System
Beáta Mária Benkő1, Mariam Majida Shokoya1, Dorottya Moldvai2, Anna Sebestyén2, Katalin Dezső3, Gergő Tóth4, Lajos Szente5, Romána Zelkó1, István Sebe1
1: University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary
2: Tumor Biology, Cell and Tissue Culture Laboratory, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26., Budapest 1085, Hungary
3: Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
4: Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre Str. 7-9., Budapest 1092, Hungary
5: CycloLab Cyclodextrin Research & Development Laboratory Ltd., Illatos út 7, Budapest 1097, Hungary
Poszter
Poster Session III. - H: Pharmaceutical Sciences and Health Technologies
Hungarian
Pharmaceutical Sciences and Health Technologies
Introduction: Disulfiram (DS), primarily used for alcoholism treatment, has potential as a non-chemotherapeutic adjuvant anticancer agent. However, clinical trials of orally administered DS have shown unsatisfactory anticancer efficacy due to poor solubility and rapid metabolism, which adversely affect bioavailability and limit therapeutic concentrations in target tissues.
Aim: In the realm of technological advancements, the main objective is the development of minimal-invasive pharmaceutical forms, bypassing the first pass effect, containing DS and cyclodextrins (CD) inclusion complexes with e.g., nasal, transdermal, or local applications to improve the anticancer repositioning. Aligned with the outlined pharmaceutical development strategy, the secondary aim is the assessment of CD-encapsulated DS activity on selected cancer cell lines.
Methods: CD inclusion complexes were studied for solubility and stability enhancement. Solubility study and solid-state characterization of the inclusion complexes were assessed to determine the suitable combination. Throughout the different cancer cell lines` characteristics and drug`s unspecific antitumor activity, the proliferation inhibitory effects of the CD encapsulated DS, have been studied, revealing interesting dose-independent characteristics.
Results: Inclusion complexation DS with CDs enhances its solubility and, consequently, its bioavailability. The CD-encapsulated DS demonstrated intriguing dose-independent effects across various cancer cell lines. The remarkable sensitivity of the studied A2058 and B16-F10 melanoma cell lines justifies further pharmaceutical technological approaches, thus the development extends to investigating transdermal and nasal delivery systems capable of overcoming poor bioavailability and maximizing targeted tissue delivery.
Conclusions: Repositioning DS involves both clinical and technological considerations. Parenteral formulations with molecularly encapsulated DS improve the drug delivery. The IC50 values varied significantly among cell lines, with both melanoma lines showing high sensitivity to low doses of DS. This ability to induce cytotoxicity suggests potential for combination therapies.
Funding: Supported by the EKÖP-2024-128 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.
Semmelweis University
István Sebe
I do not give consent to the publication of my abstract on the website of the congress.
in doctoral studies after complex exam (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
7451
14:48
14:54