Semi-solid extrusion 3D printing of functionalized polyethylene oxide gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort (Leonurus cardiaca L.) dry extract

Authors

DOI:

https://doi.org/10.15587/2519-4852.2024.299205

Keywords:

benzodiazepine derivative, motherwort extract, nanofibers, oleogel, polyethylene oxide, 3D printing

Abstract

Anxiety disorders are the most prevalent psychiatric disorders and are associated with a high burden of illness. Combining synthetic and native-origin compounds in treating such disorders could provide true benefits in terms of therapeutic efficacy. In the present study, we combined triazolobenzodiazepine and motherwort (Leonurus cardiaca L.) dry extract for such applications.

The aim. The aim of this study was to develop aqueous polyethylene oxide (PEO) composite gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort herb dry extract for semi-solid extrusion (SSE) 3D printing. The printability of such gels and the physicochemical properties of the final 3D-printed drug preparations were investigated.

Materials and methods. A new drug substance, 1,2,3-triazolo-1,4-benzodiazepine (MA-253) was synthesized and used to formulate oleogels and electrospun nanofibers for 3D printing. The plant-origin dry extract was prepared from a motherwort tincture and valine. The aqueous PEO gels loaded with a synthetic drug (MA-253) containing nanofibers and a valine-modified motherwort extract were prepared and subsequently used in the SSE 3D printing experiments. The homogeneity, viscosity and 3D printability of composite PEO gels were verified. The phytochemical assay of flavonoids in the 3D-printed drug preparations was conducted with the European pharmacopoeia spectrophotometric method.

Research results. Three experimental gel formulations loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort dry extract were developed and tested for the SSE 3D printing applications. The present three gels showed good SSE 3D printability without any significant printing flaws. The SSE 3D-printed lattices prepared from the aqueous PEO gels containing 100 mg/ml of motherwort extract showed the most promising 3D printing performance. The 3D-printed drug preparations were entirely dissolved in purified water (22±2 °C) within 20 minutes, thus suggesting their applicability in oral administration.

Conclusions. Novel aqueous PEO gel formulations loaded with nanofibrous 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort herb extract are feasible for pharmaceutical SSE 3D printing. The present composite PEO gels enable the preparation of printed oral immediate-release drug delivery systems for new triazolobenzodiazepine derivatives and a drug therapy supportive plant extract

Supporting Agency

  • Estonian Research Council grant (PRG1903), CurifyLabs project (VMVFA22189), and the European Union in the MSCA4Ukraine project “Design and development of 3D-printed medicines for bioactive materials of Ukrainian and Estonian medicinal plants origin” [ID number 1232466].

Author Biographies

Iryna Botsula, National University of Pharmacy

Postgraduate Student

Department of Clinical Pharmacology and Clinical Pharmacy

Igor Kireyev, National University of Pharmacy

Doctor of Medical Sciences, Professor, Head of Department

Department of Clinical Pharmacology and Clinical Pharmacy

Oleh Koshovyi, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor

Department of Pharmacognosy

Jyrki Heinämäki, University of Tartu

PhD, Professor

Institute of Pharmacy

Raal Ain, University of Tartu

PhD, Professor

Institute of Pharmacy

Maryna Mazur, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

Technician of Department

Department of Organic and Bioorganic Chemistry

Research Department of Chemistry of Functional Materials

Valentyn Chebanov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

Doctor of Chemical Sciences, Professor, First Deputy General Director

Department of Applied Chemistry

Department Director

Research Department of Chemistry of Functional Materials

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Semi-solid extrusion 3D printing of functionalized polyethylene oxide gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort (Leonurus cardiaca L.) dry extract

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Published

2024-02-29

How to Cite

Botsula, I., Kireyev, I., Koshovyi, O., Heinämäki, J., Ain, R., Mazur, M., & Chebanov, V. (2024). Semi-solid extrusion 3D printing of functionalized polyethylene oxide gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort (Leonurus cardiaca L.) dry extract. ScienceRise: Pharmaceutical Science, (1(47), 40–48. https://doi.org/10.15587/2519-4852.2024.299205

Issue

No. 1(47) (2024)

Section

Pharmaceutical Science

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Copyright (c) 2024 Iryna Botsula, Igor Kireyev, Oleh Koshovyi, Jyrki Heinämäki, Raal Ain, Maryna Mazur, Valentyn Chebanov

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