Development of niosomal nanoparticles loaded with cisplatin and vorinostat combination for cancer therapy
Hazar Ali, Zainab Lafi, Naeem Shalan
Abstract
Cisplatin (CIS) remains a cornerstone of chemotherapy but is limited by resistance and systemic toxicity. Combining DNA-damaging agents with epigenetic modulators such as vorinostat (VOR) offers a promising strategy to enhance efficacy. However, the co-delivery of these drugs is challenging due to their distinct physicochemical properties. The aim was to develop and characterize niosomal nanoparticles co-loaded with CIS and VOR (NIO-CIS-VOR) and to assess their physicochemical characteristics and in vitro anticancer activity.
Introduction
Cisplatin (CIS) remains one of the most widely used chemotherapeutic agents; however, its clinical success is hindered by resistance and dose-limiting toxicity [1]. Recent approaches suggest that combination therapy with histone deacetylase inhibitors (HDACIs), such as Vorinostat (VOR), may overcome these limitations by modulating epigenetic pathways and sensitizing cancer cells to chemotherapy [2,3].
Materials and Methods
2.1 Materials
Cisplatin Powder (CAS No. 5663-27-1) and Vorinostat (N1-Hydroxy-NB-Phenyloctanediamide CAS No. 149647-78-9) powder were purchased from certified commercial suppliers (Sigma-Aldrich, St. Louis, MO, USA). Both compounds were of analytical grade and were used without further modification. Non-ionic surfactants (Tween 80), cholesterol, ethanol, and analytical-grade solvents were used for formulation.
Results
3.1. High-Performance Liquid Chromatography (HPLC)
The linearity of the developed method was also validated by creating calibration curves using standard solutions across a concentration range of 0.015 and 1 mg/mL for both CIS and VOR. Linearity testing is essential to establish that the response of the detector (i.e., the peak area) is directly proportional to the concentration of the analyte within this range.
Discussion
The encapsulation efficiency (EE%) results demonstrated that CIS was entrapped at significantly higher levels [18] than VOR in the prepared niosomal formulations. Specifically, the NIO-CIS formulation exhibited an encapsulation efficiency (EE%) of 91.35% ± 4.4, whereas the NIO-VOR formulation showed a lower EE% of 58.1% ± 5.2. In the co-loaded NIO-CIS-VOR formulation, the EE% of CIS decreased slightly to 89.3% ± 6.1, while the EE% of VOR was reduced to 52.1% ± 3.8.
Conclusion
In the current study, the design, characterization, and in vitro evaluation of niosomal nanoparticles co-loaded with CIS and VOR were successfully demonstrated as a novel strategy for cancer therapy. The developed formulation utilized the ethanol injection method to encapsulate both a hydrophilic (CIS) and a hydrophobic (VOR) agent within a non-ionic surfactant-based vesicle system.
Citation: Ali H, Lafi Z, Shalan N (2026) Development of niosomal nanoparticles loaded with cisplatin and vorinostat combination for cancer therapy. PLoS One 21(2): e0342344. https://doi.org/10.1371/journal.pone.0342344
Editor: Aliasgar Shahiwala, Dubai Pharmacy College, UNITED ARAB EMIRATES
Received: August 29, 2025; Accepted: January 20, 2026; Published: February 6, 2026
Copyright: © 2026 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: all data were included in the manuscript.
Funding: This study was funded by Al-Ahliyya Amman University as student, master’s degree research.
Competing interests: Authors declared no conflict of interest in this study.
