Benkő, Beáta Mária and Tóth, Gergő and Moldvai, Dorottya and Kádár, Szabina and Szabó, Edina and Szabó, Zoltán-István and Mazákné Kraszni, Márta and Szente, Lajos and Fiser, Béla and Sebestyén, Anna and Zelkó, Romána and Sebe, István (2024) Cyclodextrin encapsulation enabling the anticancer repositioning of disulfiram: Preparation, analytical and in vitro biological characterization of the inclusion complexes. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 657. No.-124187. ISSN 0378-5173
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Abstract
Drug repositioning is a high-priority and feasible strategy in the field of oncology research, where the unmet medical needs are continuously unbalanced. Disulfiram is a potential non-chemotherapeutic, adjuvant anticancer agent. However, the clinical translation is limited by the drug‘s poor bioavailability. Therefore, the molecular encapsulation of disulfiram with cyclodextrins is evaluated to enhance the solubility and stability of the drug. The present work describes for the first time the complexation of disulfiram with randomly methylated- β-cyclodextrin. A parallel analytical andin vitrobiological comparison of disulfiram inclusion complexes with hydroxypropyl-β-cyclodextrin, randomly methylated-β-cyclodextrin and sulfobutylether-β-cyclodextrin is conducted. A significant drug solubility enhancement by about 1000-folds and fast dissolution in 1 min is demonstrated. Thein vitrodissolution-permeation studies and proliferation assays demonstrate the solubility- dependent efficacy of the drug. Throughout the different cancer cell lines‘ characteristics and disulfiram unspecific antitumoral activity, the inhibitory efficacy of the cyclodextrin encapsulated drug on melanoma (IC50 about 100 nM) and on glioblastoma (IC50 about 7000 nM) cell lines differ by a magnitude. This pre-formulation screening experiment serves as a proof of concept of using cyclodextrin encapsulation as a platform tool for further drug delivery development in repositioning areas.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Semmelweis Science and Innovation Fund; New National Excellence Program of the Ministry for Culture and Innovation from National Research, Development and Innovation Fund [UNKP-23-3-II-SE- 95, UNKP-23-3-II-BME-88]; National Research, Development and Innovation Office, Hungary [TKP2021- NVA-14, NKFIH FK 146930, NKFI-K-142799] Funding text: This research was funded by the Semmelweis Science and Innovation Fund [I.S.: STIA-KFI 2022], by the New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund [B.M.B.: UNKP-23-3-II-SE- 95 and Sz.K.: UNKP-23-3-II-BME-88] and supported by the National Research, Development and Innovation Office, Hungary [B.F.: TKP2021- NVA-14; G.T.: NKFIH FK 146930; A.S.: NKFI-K-142799]. |
| Uncontrolled Keywords: | Disulfiram, Cyclodextrin, Anticancer, Repositioning, Glioblastoma, Melanoma |
| Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 20 Sep 2024 09:47 |
| Last Modified: | 20 Sep 2024 09:47 |
| URI: | https://real.mtak.hu/id/eprint/205320 |
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