Synergistic Cytotoxicity of Cisplatin Combined with Curcumin  and Green Tea Extract via Nanoliposomal Co-Delivery in Oral  Squamous Cell Carcinoma

Mahsa Yousefi; Mohammadreza Vejdani; Ladan Esmaeili; Seher Hasanzade; Malika Foziljonova; Makhbuba Yarmuxamedova; Yoqutkhon Tojiboyeva; Otabek Toirov; Xurshidjon Odilov; Bakhor Khakimova; Meysam Ebrahimifar

doi:10.31557/apjcb.2026.11.1.75-82

Authors

Mahsa Yousefi School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.
Mohammadreza Vejdani School of Dentistry, Babol University of Medical Sciences, Babol, Iran.
Ladan Esmaeili Yerevan State Medical University after Mkhitar Heratsi, Faculty of Stomatology, Yerevan, Armenia.
Seher Hasanzade Department of periodontology, Gazi University of Dentistry Faculty, Ankara, Türkiye.
Malika Foziljonova DSc, ass Professor, Department of Pharmaceutical technology, Institute of Pharmaceutical education and research, Tashkent, Uzbekistan.
Makhbuba Yarmuxamedova C.M.S., Associate Professor of the Department of Infection Disease, Samarkand State Medical University, Samarkand, Uzbekistan.
Yoqutkhon Tojiboyeva Teacher Assistant of Department of Pediatric Dentistry, Dental Faculty, Andijan State Medical Institute, Andijan, Uzbekistan.
Otabek Toirov PhD, Department of Materials Science and Mechanical Engineering, Tashkent State Transport University, Tashkent, Uzbekistan.
Xurshidjon Odilov Senior Teacher of Department “General Surgery”, Fergana Medical Institute of Public Health, Fergana, Republic of Uzbekistan.
Bakhor Khakimova PhD, Senior Lecturer, Department of Food Technology, Faculty of Chemical Technologies, Urgench State University Named after Abu Rayhon Biruni, Urgench, Uzbekistan.
Meysam Ebrahimifar Department of Toxicology, Faculty of Pharmacy, Islamic Azad University, Shahreza Branch, Shahreza, Iran.

DOI:

https://doi.org/10.31557/apjcb.2026.11.1.75-82

Keywords:

Keywords Oral squamous cell carcinoma (OSCC); Nanoliposomes; Cisplatin; Green tea extract; Curcumin; Synergistic cytotoxicity; Apoptosis; Drug delivery systems

Abstract

Background: Oral squamous cell carcinoma (OSCC) remains one of the most prevalent malignancies worldwide, with cisplatin-based chemotherapy limited by systemic toxicity and drug resistance. The present study aimed to enhance cisplatin efficacy through nanoliposomal co-delivery with natural antioxidants curcumin (Cur) and green tea extract (epigallocatechin gallate, EGCG).

Methods: Nanoliposomes were prepared via the thin-film hydration technique followed by sonication and extrusion, generating six formulations: cisplatin-loaded (L-Cis), curcumin-loaded (L-Cur), green tea extract-loaded (L-EGCG), cisplatin + curcumin (L-Cis/Cur), cisplatin + green tea extract (L-Cis/EGCG), and triple co-loaded nanoliposomes containing cisplatin, curcumin, and EGCG (L-Cis/Cur/EGCG) prepared according to a 1:6:6 molar ratio.

Results: Physicochemical characterization revealed nanoscale particle size (212–279 nm), uniform distribution (PDI < 0.3), negative zeta potential (−19 to −23 mV), and high encapsulation efficiencies (69–84%). Scanning electron microscopy confirmed spherical morphology with smooth, homogeneous surfaces. The MTT assay demonstrated that co-loaded and triple-loaded liposomes exhibited significantly higher cytotoxicity than single-drug formulations (p < 0.001). While L-Cis reduced cell viability to approximately 50%, L-Cur and L-EGCG showed moderate effects (~65–70% viability). Co-formulations (L-Cis/Cur and L-Cis/EGCG) further decreased viability to 25–30%, and the triple co-loaded L-Cis/Cur/EGCG (1:6:6) formulation induced the strongest cytotoxic response, consistent with synergistic drug interaction. Live/Dead fluorescence imaging corroborated these findings, showing an elevated proportion of PI-positive apoptotic cells in the co-delivery groups, particularly in the triple-loaded syste.

Conclusion: Collectively, these results demonstrate that nanoliposomal co-encapsulation of cisplatin with curcumin and green tea extract enhances cytotoxic efficacy and apoptotic activity in OSCC cells compared to single-agent systems. The optimized L-Cis/Cur/EGCG (1:6:6) formulation exhibited the most favorable physicochemical properties and biological performance, highlighting its potential as a synergistic nanocarrier platform for oral cancer therapy with improved efficacy and reduced systemic toxicity.