Abstract
This study explored the potential of poly-(lactic-co-glycolic) acid (PLGA) nanoparticles to enhance the effectiveness of anticancer treatments through combination therapy with phytol and α-bisabolol. The encapsulation efficiency of the nanoparticles was investigated, highlighting the role of ionic interactions between the drugs and the polymer. Characterization of PLGA-Phy+Bis nanoparticles was carried out using DLS with zeta potential and HR-TEM for size determination. Spectrophotometric measurements evaluated the encapsulation efficiency, loading efficiency, and in vitro drug release. FTIR analysis assessed the chemical interactions between PLGA and the drug actives, ensuring nanoparticle stability. GC-MS was employed to analyze the chemical composition of drug-loaded PLGA nanocarriers. Cytotoxicity was evaluated via the MTT assay, while Annexin V-FITC/PI staining and western blot analysis confirmed apoptotic cell death. Additionally, toxicity tests were performed on L-132 cells and in vivo zebrafish embryos. The study demonstrates high encapsulation efficiency of PLGA-Phy+Bis nanoparticles, which exhibit monodispersity and sizes of 189.3±5nm (DLS) and 268±54 nm (HR-TEM). Spectrophotometric analysis confirmed efficient drug encapsulation and release control. FTIR analysis revealed nanoparticle structural stability without chemical interactions. MTT assay results demonstrated the promising anticancer potential of all the three nanoparticle types (PLGA-Phy, PLGA-Bis, and PLGA-Phy+Bis) against lung cancer cells. Apoptosis was confirmed through Annexin V-FITC/PI staining and western blot analysis, which also revealed changes in Bax and Bcl-2 protein expression. Furthermore, the nanoparticles exhibited non-toxicity in L-132 cells and zebrafish embryo toxicity tests. PLGA-Phy+Bis nanoparticles exhibited efficient encapsulation, controlled release, and low toxicity. Apoptosis induction in A549 cells and non-toxicity in healthy cells highlight their clinical potential.
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The article contains all relevant data from the study. The original contributions are available upon request to the corresponding author for further inquiries.
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Acknowledgements
The authors thankfully acknowledge DST-FIST (Grant No. SR/FST/LSI-639/2015(C)), UGC-SAP (Grant No.F.5-1/2018/DRSII (SAP-II)), DST-PURSE (Grant No. SR/PURSE Phase 2/38 (G)), and ICMR Ad-hoc project (ISRM/Ad-hoc/31/2020-21), for providing Instrumentations and lab facilities. The authors also thank RUSA 2.0 (F. 24-51/2014-U, Policy (TNMulti-Gen), Dept of Edn, GoI).
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CK designed and conducted the experiments, with assistance from DJB in developing the methodology. SKP and NHP provided support in interpreting FTIR and GC-MS results. KPD encouraged CK to explore the topic and supervised the research findings. SJ contributed to sample preparation, while NMP and MM aided in assessing embryo toxicity. CK and KPD thoroughly reviewed the findings and jointly approved the final version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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The zebrafish embryo acute toxicity test was conducted following the guidelines and regulations of the Institutional Ethics Committee of Alagappa University, Karaikudi, India. The study was approved under the ethical approval number IAEC/AU/OCT/2021/Fish-6.
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Kiruthiga, C., Balan, D.J., Prasath, N.H. et al. Synergistic induction of apoptosis in lung cancer cells through co-delivery of PLGA phytol/α-bisabolol nanoparticles. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-023-02935-2
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DOI: https://doi.org/10.1007/s00210-023-02935-2