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Pharmaceutics
Volume 17
Issue 7
10.3390/pharmaceutics17070904
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Article

Distinct In Vitro Effects of Liposomal and Nanostructured Lipid Nanoformulations with Entrapped Acidic and Neutral Doxorubicin on B16-F10 Melanoma and Walker 256 Carcinoma Cells

by
Roxana Pop
1,†,
Mădălina Nistor
1,†,
Carmen Socaciu
1,2,
Mihai Cenariu
1,
Flaviu Tăbăran
1,
Dumitriţa Rugină
1,*,
Adela Pintea
1 and
Mihai Adrian Socaciu
2,3
1
Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
2
Department of Biotechnology, Biodiatech—Research Centre for Applied Biotechnology in Diagnosis and Molecular Therapy, 400478 Cluj-Napoca, Romania
3
Faculty of Medicine, University of Medicine and Pharmacy “Iuliu Haţieganu”, 400347 Cluj-Napoca, Romania
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2025, 17(7), 904; https://doi.org/10.3390/pharmaceutics17070904 (registering DOI)
Submission received: 19 May 2025 / Revised: 4 July 2025 / Accepted: 7 July 2025 / Published: 12 July 2025
(This article belongs to the Special Issue Dispersed System for Controlled Drug Release and Delivery—the Path to Effective Therapeutic Solutions)
Versions Notes

Abstract

Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC50 values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC50 values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations.
Keywords: doxorubicin; liposomes; nanolipid; carriers; melanoma; mammary; cells doxorubicin; liposomes; nanolipid; carriers; melanoma; mammary; cells

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MDPI and ACS Style

Pop, R.; Nistor, M.; Socaciu, C.; Cenariu, M.; Tăbăran, F.; Rugină, D.; Pintea, A.; Socaciu, M.A. Distinct In Vitro Effects of Liposomal and Nanostructured Lipid Nanoformulations with Entrapped Acidic and Neutral Doxorubicin on B16-F10 Melanoma and Walker 256 Carcinoma Cells. Pharmaceutics 2025, 17, 904. https://doi.org/10.3390/pharmaceutics17070904

AMA Style

Pop R, Nistor M, Socaciu C, Cenariu M, Tăbăran F, Rugină D, Pintea A, Socaciu MA. Distinct In Vitro Effects of Liposomal and Nanostructured Lipid Nanoformulations with Entrapped Acidic and Neutral Doxorubicin on B16-F10 Melanoma and Walker 256 Carcinoma Cells. Pharmaceutics. 2025; 17(7):904. https://doi.org/10.3390/pharmaceutics17070904

Chicago/Turabian Style

Pop, Roxana, Mădălina Nistor, Carmen Socaciu, Mihai Cenariu, Flaviu Tăbăran, Dumitriţa Rugină, Adela Pintea, and Mihai Adrian Socaciu. 2025. "Distinct In Vitro Effects of Liposomal and Nanostructured Lipid Nanoformulations with Entrapped Acidic and Neutral Doxorubicin on B16-F10 Melanoma and Walker 256 Carcinoma Cells" Pharmaceutics 17, no. 7: 904. https://doi.org/10.3390/pharmaceutics17070904

APA Style

Pop, R., Nistor, M., Socaciu, C., Cenariu, M., Tăbăran, F., Rugină, D., Pintea, A., & Socaciu, M. A. (2025). Distinct In Vitro Effects of Liposomal and Nanostructured Lipid Nanoformulations with Entrapped Acidic and Neutral Doxorubicin on B16-F10 Melanoma and Walker 256 Carcinoma Cells. Pharmaceutics, 17(7), 904. https://doi.org/10.3390/pharmaceutics17070904

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