Formulation and Investigation of CK2 Inhibitor-Loaded Alginate Microbeads with Different Excipients

Boglárka Papp; Marc Le Borgne; Florent Perret; Christelle Marminon; Liza Józsa; Ágota Pető; Dóra Kósa; Lajos Nagy; Sándor Kéki; Zoltán Ujhelyi; Ádám Pallér; István Budai; Ildikó Bácskay; Pálma Fehér

doi:10.3390/pharmaceutics15122701

Formulation and Investigation of CK2 Inhibitor-Loaded Alginate Microbeads with Different Excipients

Pharmaceutics. 2023 Nov 29;15(12):2701. doi: 10.3390/pharmaceutics15122701.

Authors

Boglárka Papp^{1

2}, Marc Le Borgne³, Florent Perret⁴, Christelle Marminon³, Liza Józsa^{1

2}, Ágota Pető^{1

2}, Dóra Kósa^{1

2}, Lajos Nagy⁵, Sándor Kéki⁵, Zoltán Ujhelyi^{1

6}, Ádám Pallér¹, István Budai⁷, Ildikó Bácskay^{1

2

6}, Pálma Fehér^{1

6}

Affiliations

¹ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, H-4032 Debrecen, Hungary.
² Institute of Healthcare Industry, University of Debrecen, Nagyerdei Körút 98, H-4032 Debrecen, Hungary.
³ Small Molecules for Biological Targets Team, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, CNRS 5286, INSERM 1052, Université Claude Bernard Lyon 1, Univ Lyon, 69373 Lyon, France.
⁴ Univ Lyon, Université Lyon 1, CNRS, INSA, CPE, ICBMS, 69622 Lyon, France.
⁵ Department of Applied Chemistry, Faculty of Science and Technology, Institute of Chemistry, University of Debrecen, Egyetem Tér 1, H-4032 Debrecen, Hungary.
⁶ Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, H-4032 Debrecen, Hungary.
⁷ Faculty of Engineering, University of Debrecen, Ótemető Utca 2-4, H-4028 Debrecen, Hungary.

Abstract

The aim of this study was to formulate and characterize CK2 inhibitor-loaded alginate microbeads via the polymerization method. Different excipients were used in the formulation to improve the penetration of an active agent and to stabilize our preparations. Transcutol^® HP was added to the drug-sodium alginate mixture and polyvinylpyrrolidone (PVP) was added to the hardening solution, alone and in combination. To characterize the formulations, mean particle size, scanning electron microscopy analysis, encapsulation efficiency, swelling behavior, an enzymatic stability test and an in vitro dissolution study were performed. The cell viability assay and permeability test were also carried out on the Caco-2 cell line. The anti-oxidant and anti-inflammatory effects of the formulations were finally evaluated. The combination of Transcutol^® HP and PVP in the formulation of sodium alginate microbeads could improve the stability, in vitro permeability, anti-oxidant and anti-inflammatory effects of the CK2 inhibitor.

Keywords: CK2 inhibitor DMAT; Transcutol® HP; alginate microbeads; polyvinylpyrrolidone; protein kinase CK2.

Grants and funding

The work was supported by 2019-2.1.11-TÉT-2020-00098, titled ‘Formulation of kinase-inhibitor microparticles in glioblastoma brain tumor therapy’. Project no. TKP2021-EGA-18 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. This research was also funded by “Institut Convergence PLAsCAN”, ANR-17-CONV-0002.