Download PDF
Planta Med 2019; 85(03): 258-265
DOI: 10.1055/a-0732-5757
Formulation and Delivery Systems of Natural Products
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of Crocin and Crocetin

Carmelo Puglia
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Debora Santonocito
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Teresa Musumeci
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Venera Cardile
2   Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Adriana Carol Eleonora Graziano
2   Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Loredana Salerno
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Giuseppina Raciti
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Lucia Crascì
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Anna Maria Panico
1   Department of Drug Sciences, University of Catania, Catania, Italy
,
Giovanni Puglisi
1   Department of Drug Sciences, University of Catania, Catania, Italy
› Author Affiliations
Further Information

Publication History

received 03 July 2018
revised 20 August 2018

accepted 27 August 2018

Publication Date:
11 September 2018 (online)

   Permissions and Reprints

Abstract

Crocin and crocetin are two interesting constituents of saffron (Crocus sativus) that possess important biological activities. Their use as therapeutic agents is strongly compromised by a scarce stability, poor absorption, and low bioavailability. Therefore, to improve these unfavorable features, the aim of the present work has been to apply a nanotechnological approach based on the formulation of solid lipid nanoparticles containing crocin and crocetin. Solid lipid nanoparticles were formulated according to crocin and crocetin chemical properties, using a variation of the quasi-emulsion solvent diffusion method to formulate crocin-solid lipid nanoparticles, while crocetin-solid lipid nanoparticles were prepared following the solvent diffusion method. Morphology and dimensional distribution of solid lipid nanoparticles have been characterized by differential scanning calorimetry and photon correlation spectroscopy, respectively, while the effect of drug incorporation versus time has been studied by Turbiscan technology. In order to verify the role of the nanotechnological approach on the biological activities of crocin and crocetin, the antioxidant and antiproliferative effects of these carotenoids once incorporated in lipid nanoparticles have been evaluated. For this aim, the oxygen radical absorbance capacity assay and the MTT test were used, respectively.

The results pointed out the formulation of nanometric dispersions endowed with high homogeneity and stability, with an encapsulation efficiency ranging from 80 (crocetin-solid lipid nanoparticles) to 94% (crocin-crocetin). The oxygen radical absorbance capacity assay evidenced an interesting and prolonged antioxidant activity of crocin and crocetin once encapsulated in solid lipid nanoparticles, while the nanoencapsulation strategy showed a different mechanism in ameliorating the cytotoxic effect of these two substances.

Key words

Crocus sativus - Iridaceae - solid lipid nanoparticles - Turbiscan analysis - antioxidant - cytotoxic
 

  • References

  • 1 Rahaiee S, Hashemi M, Shojaosadati SA, Moini S, Razavi SH. Nanoparticles based on crocin loaded chitosan-alginate biopolymers: Antioxidant activities, bioavailability and anticancer properties. Int J Biol Macromol 2017; 99: 401-408
    CrossrefPubMedGoogle Scholar
  • 2 Rahaiee S, Moini S, Hashemi M, Shojaosadati SA. Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review. J Food Sci Technol 2015; 52: 1881-1888
    CrossrefPubMedGoogle Scholar
  • 3 Abdullaev FI. Biological effects of saffron. Biofactors 1993; 4: 83-86
    PubMedGoogle Scholar
  • 4 Gutheil WG, Reed G, Ray A, Anant S, Dhar A. Crocetin: an agent derived from saffron for prevention and therapy for cancer. Curr Pharm Biotechnol 2012; 13: 173-179
    CrossrefPubMedGoogle Scholar
  • 5 Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, Jung WS, Cho KH, Park JH, Kang I, Hong JW, Lee EH. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 2010; 648: 110-116
    CrossrefPubMedGoogle Scholar
  • 6 Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother 2018; 98: 333-337
    CrossrefPubMedGoogle Scholar
  • 7 Finley JW, Gao S. A perspective on Crocus sativus L. (saffron) constituent crocin: a potent water-soluble antioxidant and potential therapy for Alzheimerʼs disease. J Agric Food Chem 2017; 65: 1005-1020
    CrossrefPubMedGoogle Scholar
  • 8 Esposito E, Drechsler M, Mariani P, Panico AM, Cardile V, Crascì L, Carducci F, Graziano ACE, Cortesi R, Puglia C. Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.). Mater Sci Eng C Mater Biol Appl 2017; 71: 669-677
    CrossrefPubMedGoogle Scholar
  • 9 Baghishani F, Mohammadipour A, Hosseinzadeh H, Hosseini M, Ebrahimzadeh-Bideskan A. The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin. Metab Brain Dis 2018; 33: 907-916
    CrossrefPubMedGoogle Scholar
  • 10 Wang X, Yuan B, Cheng B, Liu Y, Zhang B, Wang X, Lin X, Yang B, Gong G. Crocin alleviates myocardial ischemia/reperfusion-induced endoplasmic reticulum stress via regulation of MIR-34A/SIRT1/NRF2 pathway. Shock 2018; DOI: 10.1097/SHK.0000000000001116.
    CrossrefPubMedGoogle Scholar
  • 11 Li X, Jiang C, Zhu W. Crocin reduces the inflammation response in rheumatoid arthritis. Biosci Biotechnol Biochem 2017; 81: 891-898
    CrossrefPubMedGoogle Scholar
  • 12 Yao C, Liu BB, Qian XD, Li LQ, Cao HB, Guo QS, Zhou GF. Crocin induces autophagic apoptosis in hepatocellular carcinoma by inhibiting Akt/mTOR activity. Onco Targets Ther 2018; 11: 2017-2028
    CrossrefPubMedGoogle Scholar
  • 13 Kim B, Park B. Saffron carotenoids inhibit STAT3 activation and promote apoptotic progression in IL-6-stimulated liver cancer cells. Oncol Rep 2018; 39: 1883-1891
    PubMedGoogle Scholar
  • 14 Tsimidou M, Biliaderis CG. Kinetic studies of saffron (Crocus sativus L.) quality deterioration. J Agric Food Chem 1997; 45: 2890-2898
    CrossrefPubMedGoogle Scholar
  • 15 Tsimidou M, Tsatsaroni E. Stability of saffron pigments in aqueous extracts. J Food Sci 1993; 58: 1073-1075
    CrossrefPubMedGoogle Scholar
  • 16 Asai A, Nakano T, Takahashi M, Nagao A. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem 2005; 53: 7302-7306
    CrossrefPubMedGoogle Scholar
  • 17 Kanakis CD, Tarantilis PA, Tajmir-Riahi HA, Polissiou MG. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J Agric Food Chem 2007; 55: 970-977
    CrossrefPubMedGoogle Scholar
  • 18 Puglia C, Rizza L, Drechsler M, Bonina F. Nanoemulsions as vehicles for topical administration of glycyrrhetic acid: characterization and in vitro and in vivo evaluation. Drug Deliv 2010; 17: 123-129
    CrossrefPubMedGoogle Scholar
  • 19 Tapeinos C, Battaglini M, Ciofani G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J Control Release 2017; 264: 306-332
    CrossrefPubMedGoogle Scholar
  • 20 Puglia C, Offerta A, Carbone C, Bonina F, Pignatello R, Puglisi G. Lipid nanocarriers (LNC) and their applications in ocular drug delivery. Curr Med Chem 2015; 22: 1589-1602
    CrossrefPubMedGoogle Scholar
  • 21 Gallarate M, Trotta M, Battaglia L, Chirio D. Preparation of solid lipid nanoparticles from W/O/W emulsions: preliminary studies on insulin encapsulation. J Microencapsul 2009; 26: 394-402
    CrossrefPubMedGoogle Scholar
  • 22 Kawashima Y, Niwa T, Handa T, Takeuchi H, Iwamoto T, Itoh Y. Preparation of prolonged-release spherical micro-matrix of ibuprofen with acrylic polymer by the emulsion-solvent diffusion method for improving bioavailability. Chem Pharm Bull 1989; 37: 425-429
    CrossrefPubMedGoogle Scholar
  • 23 Carbone C, Campisi A, Manno D, Serra A, Spatuzza M, Musumeci T, Bonfanti R, Puglisi G. The critical role of didodecyldimethylammonium bromide on physico-chemical, technological and biological properties of NLC. Colloids Surf B Biointerfaces 2014; 121: 1-10
    CrossrefPubMedGoogle Scholar
  • 24 Geszke-Moritz M, Moritz M. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies. Mater Sci Eng C Mater Biol Appl 2016; 68: 982-994
    CrossrefPubMedGoogle Scholar
  • 25 Das I, Chakrabarty RN, Das S. Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice. Asian Pacific J Cancer Prev 2004; 5: 70-76
    PubMedGoogle Scholar
  • 26 Abdullaev F. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med 2002; 227: 20-25
    CrossrefPubMedGoogle Scholar
  • 27 Takahashi M, Harada K. Method for the purification of crocetin. Japan Patent WO2004078695, 2004
    PubMedGoogle Scholar
  • 28 Puglia C, Offerta A, Tirendi GG, Tarico MS, Curreri S, Bonina F, Perrotta RE. Design of solid lipid nanoparticles for caffeine topical administration. Drug Deliv 2016; 23: 36-40
    CrossrefPubMedGoogle Scholar
  • 29 Lage M, Cantrell CL. Quantification of saffron (Crocus sativus L.) metabolites crocins, picrocrocin and safranal for quality determination of the spice grown under different environmental Moroccan conditions. Sci Hortic 2009; 121: 366-373
    CrossrefPubMedGoogle Scholar
  • 30 Puglia C, Frasca G, Musumeci T, Rizza L, Puglisi G, Bonina F, Chiechio S. Curcumin loaded NLC induces histone hypoacetylation in the CNS after intraperitoneal administration in mice. Eur J Pharm Biopharm 2012; 81: 288-293
    CrossrefPubMedGoogle Scholar