Kaempferol-loaded mucoadhesive nanoemulsion for intranasal administration reduces glioma growth in vitro
Open accessAbstract
In order to search for new approaches to treat glioma, intranasal administration has been proposed as an alternative route to deliver drugs into the brain. Among the drug alternatives, kaempferol (KPF) has been reported to induce glioma cell death. This study aimed to prepare nanoemulsions containing KPF with and without chitosan to investigate their potential for brain delivery following intranasal administration, and to evaluate their antitumor activity against glioma cells. KPF-loaded nanoemulsion (KPF-NE) and KPF-loaded mucoadhesive nanoemulsion (KPF-MNE) were prepared by high-pressure homogenization technique and were characterized for their globule size, zeta potential, drug content, pH, viscosity, mucoadhesive strength and morphology. KPF from KPF-MNE showed significantly higher permeation across the mucosa in ex vivo diffusion studies. Histopathological examination suggests both nanoemulsions to be safe for the nasal mucosa and able to preserve KPF antioxidant capability. KPF-MNE enhanced significantly the amount of drug into rat's brain following intranasal administration (5- and 4.5-fold higher than free drug and KPF-NE, respectively). In addition, KPF-MNE reduced C6 glioma cell viability through induction of apoptosis to a greater extent than either free KPF or KPF-NE. The mucoadhesive nanoemulsion developed for intranasal administration may be a promising system for delivery to the brain, and KPF-MNE is a candidate for further antiglioma trials.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reduced C6 glioma cell viability through induction of apoptosis was obtained from nanoemulsions containing chitosan to a greater extent than from free drug solution or nanoemulsion without chitosan.
“A reduced C6 glioma cell viability through induction of apoptosis was obtained from NEs containing chitosan to a greater extent than either free drug solution or NE without chitosan.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [74]
Kaempferol nanoemulsions showed no toxicity towards nasal mucosa, and ex vivo permeation was higher in formulations containing chitosan than in those without.
“The NEs showed no toxicity towards nasal mucosa, and ex vivo permeation was higher in the formulations containing chitosan in respect to those without.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [74]
The drug concentration in brain tissue after nasal administration of the kaempferol nanoemulsion containing chitosan was significantly higher than with nanoemulsions without chitosan or drug solutions.
“The drug concentration (ng/g of tissue) in brain tissue after nasal administration of the NE formulation containing chitosan was found to be significantly higher with respect to NEs without chitosan or drug solutions.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [74]
Kaempferol-loaded nanoemulsions showed nanometric globule size, high loading capacity and entrapment efficiency, and preserved the antioxidant potential of kaempferol.
“Results showed nanometric globule size, high loading capacity and entrapment efficiency, and NEs were able to preserve the antioxidant potential of kaempferol.”
From Nanoemulsions for “Nose-to-Brain” Drug Delivery (2019) · cites this paper as [74]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stupp, R., Hegi, M. E., Mason, W. P., van den Bent, M. J., TAPHOORN, M. J. B., Janzer, R. C., Ludwin, S. K., Allgeier, A., Fisher, B., Bélanger, K., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70025-7 · Cited by 7,667 · see citing works
The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles
Fröhlich, E. (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s36111 · Cited by 2,496 · see citing works
Nanocarriers’ entry into the cell: relevance to drug delivery
Hillaireau, H., & Couvreur, P. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0053-z · Cited by 1,549 · see citing works
A Review on the Dietary Flavonoid Kaempferol
Calderón‐Montaño, J. M., Burgos‐Morón, E., Pérez‐Guerrero, C., & López‐Lázaro, M. (2011) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955711795305335 · Cited by 1,391 · see citing works
Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma
Van Meir, E. G., Hadjipanayis, C. G., Norden, A. D., Shu, H. K., Wen, P. Y., & Olson, J. J. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20069 · Cited by 1,372 · see citing works
THE UNITED STATES PHARMACOPEIA.
Hatcher, R. A. (1908) · JAMA · doi:10.1001/jama.1908.25310270030002f · Cited by 1,259 · see citing works
Primary brain tumours in adults
Ricard, D., Idbaïh, A., Ducray, F., Lahutte, M., Hoang‐Xuan, K., & Delattre, J. (2012) · The Lancet · doi:10.1016/s0140-6736(11)61346-9 · Cited by 1,200 · see citing works
A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention
Chen, A. Y., & Chen, Y. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.11.139 · Cited by 996 · see citing works
Chitosan-based drug delivery systems
Bernkop‐Schnürch, A., & Dünnhaupt, S. (2012) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2012.04.007 · Cited by 994 · see citing works
Transport of drugs from the nasal cavity to the central nervous system
Illum, L. (2000) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(00)00087-7 · Cited by 907 · see citing works
Primary brain tumours in adults
Béhin, A., Hoang‐Xuan, K., Carpentier, A. F., & Delattre, J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12328-8 · Cited by 756 · see citing works
Nanoparticles for direct nose-to-brain delivery of drugs
Mistry, A., Stolnik, S., & Illum, L. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.06.019 · Cited by 734 · see citing works
Chitosan-based delivery systems for protein therapeutics and antigens
Amidi, M., Mastrobattista, E., Jiskoot, W., & Hennink, W. E. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.11.009 · Cited by 622 · see citing works
Kaempferol and inflammation: from chemistry to medicine
Devi, K. P., Malar, D. S., Nabavi, S. F., Sureda, A., Xiao, J., Nabavi, S. M., & Daglia, M. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.05.002 · Cited by 619 · see citing works
Pardeshi, C. V., & Belgamwar, V. S. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.790887 · Cited by 482 · see citing works
Sultana, B., & Anwar, F. (2008) · Food Chemistry · doi:10.1016/j.foodchem.2007.11.053 · Cited by 467 · see citing works
Chitosan in nasal delivery systems for therapeutic drugs
Casettari, L., & Illum, L. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.05.003 · Cited by 448 · see citing works
Intranasal nanoemulsion based brain targeting drug delivery system of risperidone
Kumar, M., Misra, A., Babbar, A. K., Mishra, A. K., Mishra, P., & Pathak, K. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.03.029 · Cited by 435 · see citing works
Permeability issues in nasal drug delivery
Arora, P., Sharma, S., & Garg, S. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02452-2 · Cited by 426 · see citing works
Strategy for effective brain drug delivery
Alam, M. I., Beg, S., Samad, A., Baboota, S., Kohli, K., Ali, J., Ahuja, A., & Akbar, M. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.05.003 · Cited by 415 · see citing works
Rothwell, J. A., Day, A. J., & Morgan, M. R. A. (2005) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0483669 · Cited by 329 · see citing works
Sood, S., Jain, K., & Gowthamarajan, K. (2014) · Colloids and Surfaces B: Biointerfaces · doi:10.1016/j.colsurfb.2013.09.030 · Cited by 289 · see citing works
Tight junction modulation by chitosan nanoparticles: Comparison with chitosan solution
Vllasaliu, D., Exposito-Harris, R., Heras, Á., Casettari, L., Garnett, M. C., Illum, L., & Stolnik, S. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.08.020 · Cited by 253 · see citing works
Kaempferol induces apoptosis in glioblastoma cells through oxidative stress
Sharma, V., Joseph, C., Ghosh, S. K., Agarwal, A., Mishra, M. K., & Sen, E. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0788 · Cited by 244 · see citing works
Zhu, L., Ma, J., Jia, N., Zhao, Y., & Shen, H. (2008) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2008.07.020 · Cited by 211 · see citing works
Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats
Barve, A., Chen, C., Hebbar, V., Desiderio, J., Saw, C. L. L., & Kong, A. T. (2009) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.677 · Cited by 203 · see citing works
Chen, Z., Sun, J., Chen, H.-X., Xiao, Y., Liu, D., Chen, J., Cai, H. Y., & Cai, B. (2010) · Fitoterapia · doi:10.1016/j.fitote.2010.06.028 · Cited by 159 · see citing works
Woensel, M. V., Wauthoz, N., Rosière, R., Amighi, K., Mathieu, V., Lefranc, F., Gool, S. V., & Vleeschouwer, S. D. (2013) · Cancers · doi:10.3390/cancers5031020 · Cited by 158 · see citing works
Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles
Chuah, L., Roberts, C. J., Billa, N., Abdullah, S., & Rosli, R. (2014) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2014.01.007 · Cited by 156 · see citing works
Caddeo, C., Manconi, M., Fadda, A. M., et al. (2013) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2013.06.016 · Cited by 144 · see citing works
Curcumin-Loaded N , O -Carboxymethyl Chitosan Nanoparticles for Cancer Drug Delivery
Anitha, A., Maya, S., Deepa, N., et al. (2012) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/092050611x581534 · Cited by 141 · see citing works
Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells
Choi, E. J., & Ahn, W. S. (2008) · Nutrition Research and Practice · doi:10.4162/nrp.2008.2.4.322 · Cited by 136 · see citing works
Shah, B. M., Misra, M., Shishoo, C. J., & Padh, H. (2014) · Drug Delivery · doi:10.3109/10717544.2013.878857 · Cited by 136 · see citing works
Formulation and Characterization of Nanoemulsion-Based Drug Delivery System of Risperidone
Kumar, M., Pathak, K., & Misra, A. R. (2008) · Drug Development and Industrial Pharmacy · doi:10.1080/03639040802363704 · Cited by 125 · see citing works
Liu, Y., Gao, S., Asghar, S., Liu, G., Song, J., Wang, X., Ping, Q. N., Zhang, C., & Xiao, Y. (2014) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2014.10.039 · Cited by 116 · see citing works
Liu, J., Xu, L., Liu, C., Zhang, D., Wang, S., Deng, Z., Lou, W., Xu, H., Bai, Q., & Ma, J. (2012) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2012.04.036 · Cited by 114 · see citing works
Bshara, H., Osman, R., Mansour, S., & El-Shamy, A. E.-H. A. (2013) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2013.08.027 · Cited by 113 · see citing works
Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability
Li, B., Luo, Jiang, B., Li, Jiang, & Chen, Y. (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s33670 · Cited by 107 · see citing works
Dang, Q., Song, W., Xu, D., et al. (2014) · Molecular Carcinogenesis · doi:10.1002/mc.22154 · Cited by 106 · see citing works
Jeong, J. C., Kim, M. S., Kim, T. H., et al. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9868-5 · Cited by 103 · see citing works
Kaempferol Induces Cell Cycle Arrest in HT-29 Human Colon Cancer Cells
Cho, H., & Park, J. H. Y. (2013) · Journal of Cancer Prevention · doi:10.15430/jcp.2013.18.3.257 · Cited by 100 · see citing works
Rheological study on mucoadhesivity of some nasal powder formulations
Callens, C., Ceulemans, J., Ludwig, A., et al. (2003) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(03)00024-9 · Cited by 99 · see citing works
Siegelin, M. D., Reuß, D., Habel, A., Herold‐Mende, C. C., & von Deimling, A. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0236 · Cited by 95 · see citing works
Shah, B. M., Khunt, D., Misra, M., & Padh, H. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.05.008 · Cited by 92 · see citing works
López‐Sánchez, C., Martı́n-Romero, F. J., Sun, F., et al. (2007) · Brain Research · doi:10.1016/j.brainres.2007.08.087 · Cited by 89 · see citing works
National Cancer Institute (2020) · Definitions · doi:10.32388/iw97x9 · Cited by 88 · see citing works
Carvalho, F. C., de Campos, M. L., Peccinini, R. G., et al. (2012) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2012.11.021 · Cited by 87 · see citing works
Opportunities and challenges for the nasal administration of nanoemulsions
Comfort, C., Garrastazu, G., Pozzoli, M., & Sonvico, F. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150108144655 · Cited by 69 · see citing works
Song, W., Dang, Q., Xu, D., Chen, Y., Zhu, G., Wu, K., Zeng, J., Long, Q., Wang, X., He, D., et al. (2014) · Oncology Reports · doi:10.3892/or.2014.2965 · Cited by 63 · see citing works
Influence of Formulation Viscosity on Drug Absorption Following Nasal Application in Rats
Furubayashi, T., Inoue, D., Kamaguchi, A., Higashi, Y., & Sakane, T. (2007) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.22.206 · Cited by 54 · see citing works
Bandaruk, Y., Mukai, R., & Terao, J. (2014) · Toxicology Reports · doi:10.1016/j.toxrep.2014.08.016 · Cited by 50 · see citing works
Cho, H., Ku, W.-S., Termsarasab, U., Yoon, I., Chung, C., Moon, H. T., & Kim, D. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.12.028 · Cited by 41 · see citing works
Seibert, H., Maser, E., Schweda, K., Seibert, S., & Gülden, M. (2011) · Food and Chemical Toxicology · doi:10.1016/j.fct.2011.06.055 · Cited by 38 · see citing works
Colombo, M., Melchiades, G. D. L., Figueiró, F., Battastini, A. M. O., Teixeira, H. F., & Koester, L. S. (2017) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2017.07.046 · Cited by 32 · see citing works
Self-citationInhibition of peroxide-induced radical generation by plant polyphenols in C6 astroglioma cells
Rüweler, M., Anker, A., Gülden, M., Maser, E., & Seibert, H. (2008) · Toxicology in Vitro · doi:10.1016/j.tiv.2008.02.019 · Cited by 28 · see citing works
Effects of kaempferol on the mechanisms of drug resistance in the human glioblastoma cell line T98G
Nakatsuma, A., Fukami, T., Suzuki, T., et al. (2010) · Die Pharmazie · doi:10.31083/ph.2010.9807 · Cited by 25 · see citing works
The Effect of Submicron Emulsion Systems on Transdermal Delivery of Kaempferol
Chao, Y. Y., Huang, C., Fu, L.-T., et al. (2012) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.c12-00372 · Cited by 21 · see citing works
Silva, A. O., Dalsin, E., Onzi, G. R., et al. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.09.014 · Cited by 21 · see citing works
The uptake behaviors of kaempferol and quercetin through rat primary cultured cortical neurons
Liu, R., Wang, X., Zhao, Y., et al. (2006) · Biomedical Chromatography · doi:10.1002/bmc.675 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kaempferol: A Key Emphasis to Its Anticancer Potential
Imran, M., Salehi, B., Sharifi-Rad, J., Aslam Gondal, T., Saeed, F., Imran, A., Shahbaz, M., Tsouh Fokou, P. V., Umair Arshad, M., Khan, H., et al. (2019) · Molecules · doi:10.3390/molecules24122277 · Cited by 819 · see citing works
Nanoemulsions for “Nose-to-Brain” Drug Delivery
Bonferoni, M. C., Rossi, S., Sandri, G., Ferrari, F., Gavini, E., Rassu, G., & Giunchedi, P. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11020084 · Cited by 269 · see citing works
- Authors
- Colombo, M., Figueiró, F., de Fraga Dias, A., Teixeira, H. F., Battastini, A. M. O., & Koester, L. S.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Corresponding author
- Koester, Letícia Scherer
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 543
- Issue
- 1-2
- Pages
- 214-223
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2794948476
- Cited by
- 157
- References
- 59
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 15 · 2023: 24 · 2022: 26 · 2021: 23 · 2020: 18 · 2019: 20 · 2018: 4
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CAPES
- MEC (902/2009)
- CNPq (453927/2014-9)
- INCT (2014 - 465671/2014-4)
- FAPERGS
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- kaempferol, intranasal drug delivery, glioma, brain drug delivery, chitosan, high-pressure homogenization, nasal mucosa permeation, C6 glioma cells, apoptosis, anticancer activity
- MeSH terms
- Adhesiveness, Administration, Intranasal, Animals, Antineoplastic Agents, Brain, Brain Neoplasms, Cell Survival, Emulsions, Glioma, Nasal Mucosa, Swine, Rats, Wistar, Kaempferols, Cell Line, Tumor, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
