In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting

IntroductionFrankincense has demonstrated promising in vitro anticancer activity. However, its conventional delivery methods face significant challenges due to limited oral bioavailability. To address these limitations, this study focuses on developing optimized nanoemulsions (NEs) of Frankincense o...

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Main Authors: Rayya A. Al-Balushi, Aiswarya Chaudhuri, Raghuram Kandimalla, Ashanul Haque, Khalaf M. Alenezi, Mohd. Saeed, Mohammad Changez, Thuraya Al Harthy, Mohammed Al Hinaai, Samra Siddiqui, Ashish Kumar Agrawal, Farrukh Aqil
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1403780/full
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author Rayya A. Al-Balushi
Aiswarya Chaudhuri
Raghuram Kandimalla
Ashanul Haque
Khalaf M. Alenezi
Mohd. Saeed
Mohammad Changez
Thuraya Al Harthy
Mohammed Al Hinaai
Samra Siddiqui
Ashish Kumar Agrawal
Farrukh Aqil
Farrukh Aqil
author_facet Rayya A. Al-Balushi
Aiswarya Chaudhuri
Raghuram Kandimalla
Ashanul Haque
Khalaf M. Alenezi
Mohd. Saeed
Mohammad Changez
Thuraya Al Harthy
Mohammed Al Hinaai
Samra Siddiqui
Ashish Kumar Agrawal
Farrukh Aqil
Farrukh Aqil
author_sort Rayya A. Al-Balushi
collection DOAJ
description IntroductionFrankincense has demonstrated promising in vitro anticancer activity. However, its conventional delivery methods face significant challenges due to limited oral bioavailability. To address these limitations, this study focuses on developing optimized nanoemulsions (NEs) of Frankincense oil (FO) to enhance its therapeutic efficacy.MethodsFrankincense resins were extracted and characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), identifying key metabolites including isopinocarveol, α-thujene, p-cymene, carvone, germacrene A, and various methyl esters. FO-based nanoemulsions (FO-NEs) were prepared and optimized using a 3-factor, 3-level Box-Behnken Design (BBD), with 10% FO (v/v), 40% surfactant (cremophor EL), and co-surfactant (Transcutol P). The optimized FO-NEs were evaluated for particle size, polydispersity index (PDI), zeta potential, and morphology using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Cytotoxicity, wound healing, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) assays were performed against breast cancer (MDA-MB-231, MDA-MB-231-TR) and lung cancer (A549, A549-TR, H1299) cell lines.ResultsThe optimized FO-NEs exhibited an average particle size of 65.1 ± 4.21 nm, a PDI of 0.258 ± 0.04, and a zeta potential of −22.3 ± 1.2 mV. SEM and AFM confirmed the spherical morphology of the FO-NEs. In vitro cytotoxicity studies revealed enhanced anticancer activity of FO-NEs (IC50 = 13.2 μg/mL) compared to free FO (IC50 = 22.5 μg/mL) against resistant breast cancer MDA-MB-231-TR cells. FO-NEs significantly improved cancer cell internalization, disrupted mitochondrial membrane potential, and increased ROS generation, leading to enhanced cytotoxic effects.DiscussionThe results demonstrate that nanoemulsion-based delivery significantly enhances the bioactivity and cellular uptake of frankincense oil compared to its free form. FO-NEs exhibit potent anticancer activity, particularly against drug-resistant cancer cell lines, suggesting their potential as a viable strategy for improving the therapeutic efficacy of frankincense in cancer treatment.
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spelling doaj-art-4a20bcb2a8114a409246bdfb88a4e7b22025-02-06T05:21:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.14037801403780In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targetingRayya A. Al-Balushi0Aiswarya Chaudhuri1Raghuram Kandimalla2Ashanul Haque3Khalaf M. Alenezi4Mohd. Saeed5Mohammad Changez6Thuraya Al Harthy7Mohammed Al Hinaai8Samra Siddiqui9Ashish Kumar Agrawal10Farrukh Aqil11Farrukh Aqil12Department of Basic and Applied Sciences, College of Applied and Health Sciences, A’Sharqiyah University, Ibra, OmanDepartment of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, IndiaBrown Cancer Center, University of Louisville, Louisville, KY, United StatesDepartment of Chemistry, College of Science, University of Hail, Hail, Saudi ArabiaDepartment of Chemistry, College of Science, University of Hail, Hail, Saudi ArabiaDepartment of Biology, College of Science, University of Hail, Hail, Saudi ArabiaCollege of Health Sciences, University of Buraimi, Al Buraimi, OmanDepartment of Basic and Applied Sciences, College of Applied and Health Sciences, A’Sharqiyah University, Ibra, OmanDepartment of Basic and Applied Sciences, College of Applied and Health Sciences, A’Sharqiyah University, Ibra, OmanDepartment Health Services Management, College of Public Health and Health Informatics, University of Hail, Hail, Saudi ArabiaDepartment of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, IndiaBrown Cancer Center, University of Louisville, Louisville, KY, United StatesDepartment of Medicine, University of Louisville, Louisville, KY, United StatesIntroductionFrankincense has demonstrated promising in vitro anticancer activity. However, its conventional delivery methods face significant challenges due to limited oral bioavailability. To address these limitations, this study focuses on developing optimized nanoemulsions (NEs) of Frankincense oil (FO) to enhance its therapeutic efficacy.MethodsFrankincense resins were extracted and characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), identifying key metabolites including isopinocarveol, α-thujene, p-cymene, carvone, germacrene A, and various methyl esters. FO-based nanoemulsions (FO-NEs) were prepared and optimized using a 3-factor, 3-level Box-Behnken Design (BBD), with 10% FO (v/v), 40% surfactant (cremophor EL), and co-surfactant (Transcutol P). The optimized FO-NEs were evaluated for particle size, polydispersity index (PDI), zeta potential, and morphology using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Cytotoxicity, wound healing, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) assays were performed against breast cancer (MDA-MB-231, MDA-MB-231-TR) and lung cancer (A549, A549-TR, H1299) cell lines.ResultsThe optimized FO-NEs exhibited an average particle size of 65.1 ± 4.21 nm, a PDI of 0.258 ± 0.04, and a zeta potential of −22.3 ± 1.2 mV. SEM and AFM confirmed the spherical morphology of the FO-NEs. In vitro cytotoxicity studies revealed enhanced anticancer activity of FO-NEs (IC50 = 13.2 μg/mL) compared to free FO (IC50 = 22.5 μg/mL) against resistant breast cancer MDA-MB-231-TR cells. FO-NEs significantly improved cancer cell internalization, disrupted mitochondrial membrane potential, and increased ROS generation, leading to enhanced cytotoxic effects.DiscussionThe results demonstrate that nanoemulsion-based delivery significantly enhances the bioactivity and cellular uptake of frankincense oil compared to its free form. FO-NEs exhibit potent anticancer activity, particularly against drug-resistant cancer cell lines, suggesting their potential as a viable strategy for improving the therapeutic efficacy of frankincense in cancer treatment.https://www.frontiersin.org/articles/10.3389/fphar.2025.1403780/fullfrankincense oilnanoemulsionbox-Behnken designbreast cancerdrug delivery
spellingShingle Rayya A. Al-Balushi
Aiswarya Chaudhuri
Raghuram Kandimalla
Ashanul Haque
Khalaf M. Alenezi
Mohd. Saeed
Mohammad Changez
Thuraya Al Harthy
Mohammed Al Hinaai
Samra Siddiqui
Ashish Kumar Agrawal
Farrukh Aqil
Farrukh Aqil
In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
Frontiers in Pharmacology
frankincense oil
nanoemulsion
box-Behnken design
breast cancer
drug delivery
title In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
title_full In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
title_fullStr In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
title_full_unstemmed In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
title_short In vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
title_sort in vitro anticancer effects of frankincense and its nanoemulsions for enhanced cancer cell targeting
topic frankincense oil
nanoemulsion
box-Behnken design
breast cancer
drug delivery
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1403780/full
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