Research Progress on Crocetin Solubilization Technology
Research Article
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Research Progress on Crocetin Solubilization Technology

Yiman Li 1*
1 Sichuan Agricultural University
*Corresponding author: 39218748@qq.com
Published on 24 September 2025
Journal Cover
TNS Vol.138
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-381-9
ISBN (Online): 978-1-80590-382-6
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Abstract

Crocetin is a natural carotenoid compound with biological activities such as antioxidant, antiviral and anticancer, but its poor water solubility limits its application. To improve the solubility and bioavailability of crocetin and enable it to be more active, researchers have developed a variety of different crocetin solubilization techniques. This article reviews the research on crocetin solubilization techniques in recent years, with the aim of laying the foundation for the development and industrial application of crocetin.

Keywords:

Crocetin, Solubilization, Microcapsule, Relactation, Nanoparticle, Solid dispersion

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Li,Y. (2025). Research Progress on Crocetin Solubilization Technology. Theoretical and Natural Science,138,35-42.

References

[1]. Schmidt Mathias BG, Hensel Andreas. Saffron in phytotherapy: pharmacology and clinical uses. Wiener medizinische Wochenschrift. 2007; 27: 5.

[2]. Cnr A, Sbbb C, Ravb C, Ssb A. Chemical analysis of saffron by HPLC based crocetin estimation - ScienceDirect. Journal of Pharmaceutical and Biomedical Analysis.181.

[3]. Peng FC. Protective effects of crocetin on anoxic injury in mice. Chinese Journal of New Drugs. 2007.

[4]. Guo Zi Liang LMX, Li Xiao Lin, . Crocetin: A Systematic Review. Frontiers in Pharmacology. 2022; 14: 13-.

[5]. Eidenberger T. Hydrolysate of crocetin. 2010.

[6]. Tseng TH, Chu CY, Huang JM, Shiow SJ, Wang CJ. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Letters. 1995; 97: 61-7.

[7]. Yan J, Qian Z, Sheng L, Zhao B, Yang L, Ji H, et al. Effect of crocetin on blood pressure restoration and synthesis of inflammatory mediators in heart after hemorrhagic shock in anesthetized rats. Shock. 2010; 33: 83-7.

[8]. Zhou H YX, Zhao Q, . Determination of oxygen transmission barrier of microcapsule wall by crocetin deterioration kinetics. Eur Food Res Technol. 2013; 237: 639-46.

[9]. Wong KH, Xie Y, Huang X, Kadota K, Yang Z. Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer's Disease. Scientific Reports. 2020; 10.

[10]. Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Roggero C, Vallero R. Ultrasound-Assisted Synthesis of Cyclodextrin-Based Nanosponges. 2008.

[11]. Ahmad N, Ahmad R, Naqvi AA, Ashafaq M, Alam A, Ahmad FJ, et al. The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress markers in cerebral ischemia. Artif Cells Nanomed Biotechnol. 2017.

[12]. Esfanjani AF, Jafari SM, Assadpoor E, Mohammadi A. Nano-encapsulation of saffron extract through double-layered multiple emulsions of pectin and whey protein concentrate. Journal of Food Engineering. 2015; 165: 149-55.

[13]. Esfanjani AF, Jafari SM, Assadpour E. Preparation of a multiple emulsion based on pectin-whey protein complex for encapsulation of saffron extract nanodroplets. Food Chemistry. 2017; 221: 1962-9.

[14]. Mehrnia MA, Jafari SM, Makhmal-Zadeh BS, Maghsoudlou Y. crocetin loaded nano-emulsions: Factors affecting emulsion properties in spontaneous emulsification. International Journal of Biological Macromolecules. 2016; 84: 261-7.

[15]. dong YX. Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study. Drug delivery. 2019; 26: 849-59.

[16]. Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of crocetin and Crocetin. Planta Medica. 2019; 85: 258-65.

[17]. Mertes PM, Collange O, Coliat P, Banerjee M, Pivot X. Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation. Journal of Controlled Release. 2021; 336.

[18]. Khameneh B, Halimi V, Jaafari MR, Golmohammadzadeh S. Safranal-loaded solid lipid nanoparticles: evaluation of sunscreen and moisturizing potential for topical applications. Iranian Journal of Basic Medical Sciences. 2015; 18: 58-63.

[19]. Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malaekeh-Nikouei B. Improvement of cytotoxic and apoptogenic properties of crocetin in cancer cell lines by its nanoliposomal form. Pharmaceutical Biology. 2011; 49: 1039-45.

[20]. Rastgoo M, Hosseinzadeh H, Alavizadeh H, Abbasi A, Ayati Z, Jaafari M. Antitumor activity of PEGylated nanoliposomes containing crocetin in mice bearing C26 colon carcinoma. Planta Medica. 2013; 79: 447.

[21]. Li Jinglei NJ, Wu Haishan, Park Hyun Jin, Zhao Qingsheng, Yang Liu. Middle purity soy lecithin is appropriate for food grade nanoliposome: Preparation, characterization, antioxidant and anti-inflammatory ability. Food chemistry. 2022; 389.

[22]. Langroodi FA, Ghahestani ZH, Alibolandi M, Ebrahimian M, Hashemi M. Evaluation of the effect of crocetin on antitumor activity of doxorubicin encapsulated in PLGA nanoparticles. Nanomedicine. 2016; 3: 23-34.

[23]. Hafezi Ghahestani Zohreh ALF, Mokhtarzadeh Ahad, Ramezani Mohammad, et al. Evaluation of anti-cancer activity of PLGA nanoparticles containing crocetin Artificial cells, nanomedicine, and biotechnology. 2017; 45: 955-60.

[24]. Navid, Neyshaburinezhad, Fatemeh, Kalalinia, Maryam, Hashemi. Encapsulation of crocetin into poly (lactic-co-glycolic acid) nanoparticles overcomes drug resistance in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS). Molecular biology reports.46: 6525-32.

[25]. Solgi, Mousa. Evaluation of plant-mediated Silver nanoparticles synthesis and its application in postharvest Physiology of cut Flowers. Physiology & Molecular Biology of Plants. 2014; 20: 279-85.

[26]. Thamer NA AL. reen synthesis optimization and characterization of silver nanoparticles using aqueous extract of Crocus sativus L. Int J Pharm Bio Sci 2014; 5: 759-70.

[27]. Anahita SZ HRA, Seyyed Mahdi R, . Evaluation of reciprocal pharmaceutical effects and antibacterial activity of silver nanoparticles and metha-nolic extract of Crocus sativus L. Int J Enteric Pathog. 2017; 5: 18-23.

[28]. Arefeh T, Maliheh E. BIOSYNTHESIS AND CHARACTERIZATION OF SILVER NANOPARTICLES USING AQUEOUS EXTRACT OF SAFFRON CORM AND EVALUATION OF THEIR ANTIBACTERIAL AND MUTAGENESIS ACTIVITY. 2017.

[29]. Ghodsieh, Bagherzade, Maryam, Manzari, Tavakoli, Mohmmad, et al. Green synthesis of silver nanoparticles using aqueous extract of saffron(Crocus sativus L.) wastages and its antibacterial activity against six bacteria. Asia-pacific Journal of Tropical Biomedical Sciences: English Edition. 2017: 7.

[30]. Vijayakumar R, Devi V, Adavallan K, Saranya D. Green synthesis and characterization of gold nanoparticles using extract of anti-tumor potent Crocus sativus. Physica E Low-dimensional Systems and Nanostructures. 2011; 44.

[31]. Hoshyar R, Khayati GR, Poorgholami M, Kaykhaii M. A novel green one-step synthesis of gold nanoparticles using crocetin and their anti-cancer activities. J Photochem Photobiol B. 2016: 237-42.

[32]. El-Kharrag, Rkia, Amin, Hisaindee, Soleiman, Greish, et al. Development of a therapeutic model of precancerous liver using crocetin-coated magnetite nanoparticles.

[33]. Mary, T., Shanthi, K., Vimala, Soundarapandian. PEG functionalized selenium nanoparticles as a carrier of crocetin to achieve anticancer synergism. RSC ADVANCES. 2016: 22936-49.

[34]. Inkielewicz-Stepniak, Iwona, Radomski, Witold M, Santos-Martinez, Jose M, et al. CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: Protective effect of crocetin. Toxicology in vitro: an international journal published in association with BIBRA. 2015.

[35]. Zhong Hui. Research on the Solid Dispersion Sustained-release Tablets of saffron acid. Jiangsu University. 2014.

[36]. Zhang, X. T., Ma, S. W., Wang, L., He, S. J., and Yu, J. Y. 2011. The Preparation Method of Crocetin Injection.

[37]. Wang, H. D., and Li, l. (2015). Crocetin Salt Injection and Preparation Process Thereof.

References

[1]. Schmidt Mathias BG, Hensel Andreas. Saffron in phytotherapy: pharmacology and clinical uses. Wiener medizinische Wochenschrift. 2007; 27: 5.

[2]. Cnr A, Sbbb C, Ravb C, Ssb A. Chemical analysis of saffron by HPLC based crocetin estimation - ScienceDirect. Journal of Pharmaceutical and Biomedical Analysis.181.

[3]. Peng FC. Protective effects of crocetin on anoxic injury in mice. Chinese Journal of New Drugs. 2007.

[4]. Guo Zi Liang LMX, Li Xiao Lin, . Crocetin: A Systematic Review. Frontiers in Pharmacology. 2022; 14: 13-.

[5]. Eidenberger T. Hydrolysate of crocetin. 2010.

[6]. Tseng TH, Chu CY, Huang JM, Shiow SJ, Wang CJ. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Letters. 1995; 97: 61-7.

[7]. Yan J, Qian Z, Sheng L, Zhao B, Yang L, Ji H, et al. Effect of crocetin on blood pressure restoration and synthesis of inflammatory mediators in heart after hemorrhagic shock in anesthetized rats. Shock. 2010; 33: 83-7.

[8]. Zhou H YX, Zhao Q, . Determination of oxygen transmission barrier of microcapsule wall by crocetin deterioration kinetics. Eur Food Res Technol. 2013; 237: 639-46.

[9]. Wong KH, Xie Y, Huang X, Kadota K, Yang Z. Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer's Disease. Scientific Reports. 2020; 10.

[10]. Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Roggero C, Vallero R. Ultrasound-Assisted Synthesis of Cyclodextrin-Based Nanosponges. 2008.

[11]. Ahmad N, Ahmad R, Naqvi AA, Ashafaq M, Alam A, Ahmad FJ, et al. The effect of safranal loaded mucoadhesive nanoemulsion on oxidative stress markers in cerebral ischemia. Artif Cells Nanomed Biotechnol. 2017.

[12]. Esfanjani AF, Jafari SM, Assadpoor E, Mohammadi A. Nano-encapsulation of saffron extract through double-layered multiple emulsions of pectin and whey protein concentrate. Journal of Food Engineering. 2015; 165: 149-55.

[13]. Esfanjani AF, Jafari SM, Assadpour E. Preparation of a multiple emulsion based on pectin-whey protein complex for encapsulation of saffron extract nanodroplets. Food Chemistry. 2017; 221: 1962-9.

[14]. Mehrnia MA, Jafari SM, Makhmal-Zadeh BS, Maghsoudlou Y. crocetin loaded nano-emulsions: Factors affecting emulsion properties in spontaneous emulsification. International Journal of Biological Macromolecules. 2016; 84: 261-7.

[15]. dong YX. Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study. Drug delivery. 2019; 26: 849-59.

[16]. Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of crocetin and Crocetin. Planta Medica. 2019; 85: 258-65.

[17]. Mertes PM, Collange O, Coliat P, Banerjee M, Pivot X. Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation. Journal of Controlled Release. 2021; 336.

[18]. Khameneh B, Halimi V, Jaafari MR, Golmohammadzadeh S. Safranal-loaded solid lipid nanoparticles: evaluation of sunscreen and moisturizing potential for topical applications. Iranian Journal of Basic Medical Sciences. 2015; 18: 58-63.

[19]. Mousavi SH, Moallem SA, Mehri S, Shahsavand S, Nassirli H, Malaekeh-Nikouei B. Improvement of cytotoxic and apoptogenic properties of crocetin in cancer cell lines by its nanoliposomal form. Pharmaceutical Biology. 2011; 49: 1039-45.

[20]. Rastgoo M, Hosseinzadeh H, Alavizadeh H, Abbasi A, Ayati Z, Jaafari M. Antitumor activity of PEGylated nanoliposomes containing crocetin in mice bearing C26 colon carcinoma. Planta Medica. 2013; 79: 447.

[21]. Li Jinglei NJ, Wu Haishan, Park Hyun Jin, Zhao Qingsheng, Yang Liu. Middle purity soy lecithin is appropriate for food grade nanoliposome: Preparation, characterization, antioxidant and anti-inflammatory ability. Food chemistry. 2022; 389.

[22]. Langroodi FA, Ghahestani ZH, Alibolandi M, Ebrahimian M, Hashemi M. Evaluation of the effect of crocetin on antitumor activity of doxorubicin encapsulated in PLGA nanoparticles. Nanomedicine. 2016; 3: 23-34.

[23]. Hafezi Ghahestani Zohreh ALF, Mokhtarzadeh Ahad, Ramezani Mohammad, et al. Evaluation of anti-cancer activity of PLGA nanoparticles containing crocetin Artificial cells, nanomedicine, and biotechnology. 2017; 45: 955-60.

[24]. Navid, Neyshaburinezhad, Fatemeh, Kalalinia, Maryam, Hashemi. Encapsulation of crocetin into poly (lactic-co-glycolic acid) nanoparticles overcomes drug resistance in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS). Molecular biology reports.46: 6525-32.

[25]. Solgi, Mousa. Evaluation of plant-mediated Silver nanoparticles synthesis and its application in postharvest Physiology of cut Flowers. Physiology & Molecular Biology of Plants. 2014; 20: 279-85.

[26]. Thamer NA AL. reen synthesis optimization and characterization of silver nanoparticles using aqueous extract of Crocus sativus L. Int J Pharm Bio Sci 2014; 5: 759-70.

[27]. Anahita SZ HRA, Seyyed Mahdi R, . Evaluation of reciprocal pharmaceutical effects and antibacterial activity of silver nanoparticles and metha-nolic extract of Crocus sativus L. Int J Enteric Pathog. 2017; 5: 18-23.

[28]. Arefeh T, Maliheh E. BIOSYNTHESIS AND CHARACTERIZATION OF SILVER NANOPARTICLES USING AQUEOUS EXTRACT OF SAFFRON CORM AND EVALUATION OF THEIR ANTIBACTERIAL AND MUTAGENESIS ACTIVITY. 2017.

[29]. Ghodsieh, Bagherzade, Maryam, Manzari, Tavakoli, Mohmmad, et al. Green synthesis of silver nanoparticles using aqueous extract of saffron(Crocus sativus L.) wastages and its antibacterial activity against six bacteria. Asia-pacific Journal of Tropical Biomedical Sciences: English Edition. 2017: 7.

[30]. Vijayakumar R, Devi V, Adavallan K, Saranya D. Green synthesis and characterization of gold nanoparticles using extract of anti-tumor potent Crocus sativus. Physica E Low-dimensional Systems and Nanostructures. 2011; 44.

[31]. Hoshyar R, Khayati GR, Poorgholami M, Kaykhaii M. A novel green one-step synthesis of gold nanoparticles using crocetin and their anti-cancer activities. J Photochem Photobiol B. 2016: 237-42.

[32]. El-Kharrag, Rkia, Amin, Hisaindee, Soleiman, Greish, et al. Development of a therapeutic model of precancerous liver using crocetin-coated magnetite nanoparticles.

[33]. Mary, T., Shanthi, K., Vimala, Soundarapandian. PEG functionalized selenium nanoparticles as a carrier of crocetin to achieve anticancer synergism. RSC ADVANCES. 2016: 22936-49.

[34]. Inkielewicz-Stepniak, Iwona, Radomski, Witold M, Santos-Martinez, Jose M, et al. CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: Protective effect of crocetin. Toxicology in vitro: an international journal published in association with BIBRA. 2015.

[35]. Zhong Hui. Research on the Solid Dispersion Sustained-release Tablets of saffron acid. Jiangsu University. 2014.

[36]. Zhang, X. T., Ma, S. W., Wang, L., He, S. J., and Yu, J. Y. 2011. The Preparation Method of Crocetin Injection.

[37]. Wang, H. D., and Li, l. (2015). Crocetin Salt Injection and Preparation Process Thereof.

Cite this article

Li,Y. (2025). Research Progress on Crocetin Solubilization Technology. Theoretical and Natural Science,138,35-42.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: Computational Modelling and Simulation for Biology and Medicine

ISBN: 978-1-80590-381-9(Print) / 978-1-80590-382-6(Online)
Editor: Alan Wang, Roman Bauer
Conference website: https://2025.icbiomed.org/london.html
Conference date: 19 October 2025
Series: Theoretical and Natural Science
Volume number: Vol.138
ISSN: 2753-8818(Print) / 2753-8826(Online)

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