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Article

Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas

by
Jagoda Szkudlarek
1,2,*,
Ludwika Piwowarczyk
1,*,
Violetta Krajka-Kuźniak
3,
Aleksandra Majchrzak-Celińska
3,
Szymon Tomczak
1,
Mikołaj Baranowski
4,
Rafał Pietrzyk
4,
Aneta Woźniak-Braszak
4 and
Anna Jelińska
1
1
Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 3 Rokietnicka, 60-806 Poznań, Poland
2
Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznań, Poland
3
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 3 Rokietnicka, 60-806 Poznań, Poland
4
Department of Functional Materials Physics, Institute of Physics, Faculty of Physics and Astronomy, Adam Mickiewicz University, Uniwersytetu Poznańskiego 2, 61-614 Poznań, Poland
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2025, 17(8), 1026; https://doi.org/10.3390/pharmaceutics17081026
Submission received: 31 May 2025 / Revised: 27 June 2025 / Accepted: 24 July 2025 / Published: 7 August 2025
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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Abstract

Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their low bioavailability requires nanotechnology solutions, such as liposomes. Methods: In this study, we propose the co-encapsulation of acteoside (ACT) with other natural compounds, cannabidiol (CBD) or naringenin (NG), in a cationic liposomal nanoformulation consisting of DOTAP and POPC lipids, which were prepared using the dry lipid film method. The liposomes were characterized by their physicochemical properties, including particle size, zeta potential, and polydispersity index (PDI), with additional analyses performed using 1H Nuclear Magnetic Resonance (NMR). Furthermore, biological experiments were performed with U-87 MG astrocytoma and U-138 MG GBM cell lines and non-cancerous MRC-5 lung fibroblasts using the MTT assay and evaluating the expression of Bax and Bcl-xL to evaluate their potential as anticancer agents. Conclusions: The IC50 values for the nanoformulations in U-138 MG cells at 48 h were 6 µM for ACT + CBD and 5 µM for ACT + NG. ACT and CBD or NG demonstrated a potential synergistic effect against GBM in a liposomal formulation. Notably, treatment with ACT + CBD (5 µM) and ACT + NG (5 µM) liposomal formulations significantly upregulated Bax protein level in U-138 cells at both 24 and 48 h. In parallel, ACT + CBD (5 µM) also modulated Bcl-xL protein level in both U-138 MG and U-87 MG cell lines at the same time points. The obtained nanoformulations were homogeneous and stable for 21 days, evidenced by a narrow particle size distribution, a low polydispersity index (PDI) < 0.3, and a positive zeta potential.
Keywords: acteoside; cannabidiol (CBD); naringenin; cancer; glioma; glioblastoma (GBM); anticancer; drug delivery system (DDS); liposomes acteoside; cannabidiol (CBD); naringenin; cancer; glioma; glioblastoma (GBM); anticancer; drug delivery system (DDS); liposomes
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MDPI and ACS Style

Szkudlarek, J.; Piwowarczyk, L.; Krajka-Kuźniak, V.; Majchrzak-Celińska, A.; Tomczak, S.; Baranowski, M.; Pietrzyk, R.; Woźniak-Braszak, A.; Jelińska, A. Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas. Pharmaceutics 2025, 17, 1026. https://doi.org/10.3390/pharmaceutics17081026

AMA Style

Szkudlarek J, Piwowarczyk L, Krajka-Kuźniak V, Majchrzak-Celińska A, Tomczak S, Baranowski M, Pietrzyk R, Woźniak-Braszak A, Jelińska A. Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas. Pharmaceutics. 2025; 17(8):1026. https://doi.org/10.3390/pharmaceutics17081026

Chicago/Turabian Style

Szkudlarek, Jagoda, Ludwika Piwowarczyk, Violetta Krajka-Kuźniak, Aleksandra Majchrzak-Celińska, Szymon Tomczak, Mikołaj Baranowski, Rafał Pietrzyk, Aneta Woźniak-Braszak, and Anna Jelińska. 2025. "Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas" Pharmaceutics 17, no. 8: 1026. https://doi.org/10.3390/pharmaceutics17081026

APA Style

Szkudlarek, J., Piwowarczyk, L., Krajka-Kuźniak, V., Majchrzak-Celińska, A., Tomczak, S., Baranowski, M., Pietrzyk, R., Woźniak-Braszak, A., & Jelińska, A. (2025). Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas. Pharmaceutics, 17(8), 1026. https://doi.org/10.3390/pharmaceutics17081026

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