The DOI matches its Crossref record; 66 of the 68 references it cites were found in a registry or an index.
Therapeutic efficacy and gastrointestinal biodistribution of polycationic nanoparticles for oral camptothecin delivery in early and late-stage colorectal tumor-bearing animal model
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world and is the second leading cause of cancer related deaths. New cases are increasingly diagnosed every day, but current therapeutic options are still insufficient for an effective treatment. In CRC treatment, there is a significant need for alternative treatment approaches that can both prevent relapse and provide strong antimetastatic effects as the intestines and colon are prone to metastasis to neighboring organs and tissues as well as the liver and the lung. In this study, optimized polycationic cyclodextrin (CD) nanoparticles for oral Camptothecin (CPT) delivery were comprehensively examined for in vivo performance in early and late stage tumor bearing mouse model in terms of antitumoral and antimetastatic efficacy of CPT bound to polycationic CD nanoparticles in comparison to free CPT. In addition, the gastrointestinal localization of a single administration of fluorescent dye loaded polycationic CD nanoparticles in the gastrointestinal tract at the end of 24 h after oral administration was also imaged and evaluated by in vivo imaging system against fluorescent dye intensity. Results showed that survival percentage was significantly improved in CRC-bearing mice compared to oral CPT solution, with significantly reduced colorectal tumor masses and number of liver metastatic foci (p < 0.05). It was also possible to differentiate between the effectiveness of nanoparticles in early or late stages of CRC. In vivo imaging studies have also confirmed that polycationic CD nanoparticles are able to deliver the therapeutic load up to the colon and tend to accumulate especially in tumor foci, indicating an effective local treatment strategy. In addition number of liver metastases were significantly decreased with the CPT-loaded polycationic CD nanoparticle formulation in both early and late stage tumor models. These findings indicated that CPT-loaded polycationic CD nanoparticles could be an efficient oral nanocarrier formulation for anticancer molecules that have limited application because of oral bioavailability and stability problems.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Citations
Cites
Factors affecting the clearance and biodistribution of polymeric nanoparticles
Alexis, F., Pridgen, E., Molnar, L. K., & Farokhzad, O. C. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800051m · Cited by 3,699
Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies
Keum, N., & Giovannucci, E. L. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0189-8 · Cited by 2,791
Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers
Ensign, L. M., Cone, R. A., & Hanes, J. S. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.12.009 · Cited by 1,671
The Use of Inhibitors to Study Endocytic Pathways of Gene Carriers: Optimization and Pitfalls
Vercauteren, D., Vandenbroucke, R. E., Jones, A. T., Rejman, J., Demeester, J., Smedt, S. C. D., Sanders, N. N., & Braeckmans, K. (2009) · Molecular Therapy · doi:10.1038/mt.2009.281 · Cited by 694
The utility of cyclodextrins for enhancing oral bioavailability
Carrier, R. L., Miller, L. A., & Ahmed, I. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.07.018 · Cited by 574
Hua, S., Marks, E., Schneider, J. J., & Keely, S. (2015) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2015.02.018 · Cited by 494
Gidwani, B., & Vyas, A. (2015) · BioMed Research International · doi:10.1155/2015/198268 · Cited by 490
Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature
Venditto, V. J., & Simanek, E. E. (2010) · Molecular Pharmaceutics · doi:10.1021/mp900243b · Cited by 469
Jambhekar, S. S., & Breen, P. J. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.11.017 · Cited by 403
Cyclodextrin-based gene delivery systems
Mellet, C. O., Fernández, J. M. G., & Benito, J. M. (2010) · Chemical Society Reviews · doi:10.1039/c0cs00019a · Cited by 399
Self-citationDifferential Interactions of Camptothecin Lactone and Carboxylate Forms with Human Blood Components
Mi, Z., & Burke, T. G. (1994) · Biochemistry · doi:10.1021/bi00200a013 · Cited by 298
Toxicological considerations when creating nanoparticle-based drugs and drug delivery systems
Sharma, A. K., Madhunapantula, S. V., & Robertson, G. P. (2011) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2012.637916 · Cited by 250
Colon Targeted Delivery Systems: Review of Polysaccharides for Encapsulation and Delivery
Kosaraju, S. L. (2005) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408690490478091 · Cited by 228
Adenomatous Polyps of the Colon
Levine, J. S., & Ahnen, D. J. (2006) · New England Journal of Medicine · doi:10.1056/nejmcp063038 · Cited by 201
Huang, Z.-R., Hua, S.-C., Yang, Y.-L., & Fang, J. (2008) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2008.00829.x · Cited by 201
Cyclodextrins in targeting Application to nanoparticles
Duchêne, D. (1999) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00053-2 · Cited by 180
Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin
Davis, M. E. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.05.005 · Cited by 171
Bilensoy, E., Sarısözen, C., Esendağlı, G., Doğan, A. L., Aktaş, Y., Şen, M., & Mungan, N. A. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.12.015 · Cited by 164
Self-citationLu, X., Cao, X., Zhu, Y., Wu, Z., Zhuang, X., Shao, M., Xu, Q., Zhou, Y., Ji, H., Lu, Q.-R., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0428-x · Cited by 146
Safety and efficacy of amphiphilic ß-cyclodextrin nanoparticles for paclitaxel delivery
Bilensoy, E., Gürkaynak, O., Dogan, A. L., & Hıncal, A. A. (2007) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2007.06.051 · Cited by 136
Self-citationEncapsulation of Hydrophobic Dyes in Polystyrene Micro- and Nanoparticles via Swelling Procedures
Behnke, T., Würth, C., Hoffmann, K., Hübner, M., Panne, U., & Resch‐Genger, U. (2010) · Journal of Fluorescence · doi:10.1007/s10895-010-0632-2 · Cited by 132
Çırpanlı, Y., Bilensoy, E., Doğan, A. L., & Çalış, S. (2009) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2009.04.013 · Cited by 127
Self-citationOrthotopic Mouse Model of Colorectal Cancer
Tseng, W. W., Leong, X., & Engleman, E. G. (2007) · Journal of Visualized Experiments · doi:10.3791/484 · Cited by 121
Tan, H., Gong, W.-Z., Zhou, K., Xiao, Z., Hou, F., Huang, T., Zhang, L., Dong, H., Zhang, W.-L., Liu, Y., et al. (2019) · Cancer Biology & Therapy · doi:10.1080/15384047.2019.1685157 · Cited by 119
Development of Nonsurfactant Cyclodextrin Nanoparticles Loaded With Anticancer Drug Paclitaxel
Bilensoy, E., Gürkaynak, O., Ertan, M., Şen, M., & Hıncal, A. A. (2007) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21111 · Cited by 99
Self-citationMinami, K., Hirayama, F., & Uekama, K. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js9704339 · Cited by 91
Current Status and Perspectives in the Development of Camptothecins
Zunino, F., Dallavalle, S., Laccabue, D., Beretta, G. L., Merlini, L., & Pratesi, G. (2002) · Current Pharmaceutical Design · doi:10.2174/1381612023392801 · Cited by 88
Mouse models of colorectal cancer as preclinical models
McIntyre, R. E., Buczacki, S. J. A., Arends, M. J., & Adams, D. J. (2015) · BioEssays · doi:10.1002/bies.201500032 · Cited by 86
Camptothecin-based nanodrug delivery systems
Wen, Y. F., Yingze, W., Xiaoli, L., Wei, Z., Xinhe, X., Zhongxiao, H., & Xing-jie, L. (2017) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2017.0099 · Cited by 85
Rational design of cationic cyclooligosaccharides as efficient gene delivery systems
Díaz‐Moscoso, A., Balbuena, P., Gómez-Garcı́a, M., Mellet, C. O., Benito, J. M., Gourriérec, L. L., Giorgio, C. D., Vierling, P., Mazzaglia, A., Micali, N. L., et al. (2008) · Chemical Communications · doi:10.1039/b718672j · Cited by 84
Self-citationWang, M.-J., Liu, Y., Chang, L., Wang, C.-Y., Zhao, Y.-L., Zhao, X.-B., Qian, K., Nan, X., Liu, Y., Yang, X.-M., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5003588 · Cited by 83
Polymers for colon targeted drug delivery
Rajpurohit, H., Sharma, S. K., Sharma, P. K., & Bhandari, A. (2010) · Indian Journal of Pharmaceutical Sciences · doi:10.4103/0250-474x.84576 · Cited by 82
Soluplus-Solubilized Citrated Camptothecin—A Potential Drug Delivery Strategy in Colon Cancer
Thakral, N. K., Ray, A. R., Bar‐Shalom, D., Eriksson, A. H., & MAJUMDAR, D. K. (2011) · AAPS PharmSciTech · doi:10.1208/s12249-011-9720-0 · Cited by 76
Reversing tumor stemness via orally targeted nanoparticles achieves efficient colon cancer treatment
Xu, J., Zhang, Y., Xu, J., Wang, M., Liu, G., Wang, J., Zhao, X., Qi, Y., Shi, J. Y., Cheng, K., et al. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119247 · Cited by 73
Matos, A. I., Carreira, B., Peres, C., Moura, L. I. F., Conniot, J., Fourniols, T., Scomparin, A., Martínez‐Barriocanal, Á., Arango, D., Conde, J. P., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.06.017 · Cited by 71
Zhang, Q., Zhang, F., Li, S., Liu, R., Jin, T., Dou, Y., Zhou, Z., & Zhang, J. (2019) · Theranostics · doi:10.7150/thno.34377 · Cited by 70
Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles
Rychahou, P. G., Bae, Y., Reichel, D., Zaytseva, Y. Y., Lee, E. Y., Napier, D. L., Weiss, H. L., Roller, N., Frohman, H. A., Le, A.-T., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.02.008 · Cited by 68
Ünal, S., Aktaş, Y., Benito, J. M., & Bilensoy, E. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119468 · Cited by 68
Self-citationMolecular nanoparticle-based gene delivery systems
Blanco, J. L. J., Benito, J. M., Mellet, C. O., & Fernández, J. M. G. (2017) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2017.03.012 · Cited by 64
Self-citationDu, Y., Ling, L., Ismail, M., He, W., Xia, Q., Zhou, W., Yao, C., & Li, X. (2018) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2018.08.010 · Cited by 63
Nanoparticles in Colorectal Cancer Therapy: Latest In Vivo Assays, Clinical Trials, and Patents
Cabeza, L., Perazzoli, G., Mesas, C., Jiménez‐Luna, C., Prados, J. C., Rama, A. R., & Melguizo, C. (2020) · AAPS PharmSciTech · doi:10.1208/s12249-020-01731-y · Cited by 59
Ma, Y., Fuchs, A. V., Boase, N. R. B., Rolfe, B. E., Coombes, A. G. A., & Thurecht, K. J. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.06.014 · Cited by 55
Current status of nanoscale drug delivery systems for colorectal cancer liver metastasis
Hong, Y. K., & Rao, Y. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108764 · Cited by 54
Animal models of human colorectal cancer: Current status, uses and limitations
Mittal, V. K. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i41.11854 · Cited by 53
Ünal, H., Öztürk, N., & Bilensoy, E. (2015) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.11.22 · Cited by 52
Self-citationZou, J., Li, S., Chen, Z., Lü, Z., Gao, J., Zou, J., Lin, X., Li, Y., Zhang, C., & Shen, L. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0700-0 · Cited by 51
Ünal, H., d’Angelo, I., Pagano, E., Borrelli, F., Izzo, A. A., Ungaro, F., Quaglia, F., & Bilensoy, E. (2015) · Journal of Nanoparticle Research · doi:10.1007/s11051-014-2838-8 · Cited by 48
Self-citationDevelopment of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery
Varan, G., Benito, J. M., Mellet, C. O., & Bilensoy, E. (2017) · Beilstein Journal of Nanotechnology · doi:10.3762/bjnano.8.145 · Cited by 47
Self-citationWang, Z., Chi, D., Wu, X., Wang, Y., Lin, X., Xu, Z., Liu, H., Sun, J., He, Z., & Wang, Y. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.10.037 · Cited by 47
Development of a metastatic murine colon cancer model
Terracina, K. P., Aoyagi, T., Huang, W., Nagahashi, M., Yamada, A., Aoki, K., & Takabe, K. (2015) · Journal of Surgical Research · doi:10.1016/j.jss.2015.04.030 · Cited by 45
Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles
Huarte, J., Espuelas, S., Lai, Y., He, B., Tang, J. Z., & Irache, J. M. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.04.045 · Cited by 44
Han, M. Y., He, C., Fang, Q.-L., Yang, X., Diao, Y., Xu, D., He, Q., Hu, Y., Liang, W., Yang, B., et al. (2008) · Pharmaceutical Research · doi:10.1007/s11095-008-9795-9 · Cited by 43
Gallego‐Yerga, L., de la Torre, C., Sansone, F., Casnati, A., Mellet, C. O., Fernández, J. M. G., & Ceña, V. (2020) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2020.117135 · Cited by 37
Varan, G., Öncül, S., Ercan, A., Benito, J. M., Mellet, C. O., & Bilensoy, E. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.06.021 · Cited by 35
Self-citationPilot trial of CRLX101 in patients with advanced, chemotherapy-refractory gastroesophageal cancer
Chao, J., Lin, J. L., Frankel, P. H., Clark, A. J., Wiley, D. T., Garmey, E. G., Fakih, M., Lim, D. W., Chung, V. M., Luevanos, E., et al. (2017) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo.2017.08.10 · Cited by 34
A novel mouse model for segmental orthotopic colon cancer
Alencar, H., King, R., Funovics, M. A., Stout, C. E., Weissleder, R., & Mahmood, U. (2005) · International Journal of Cancer · doi:10.1002/ijc.21185 · Cited by 32
COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW
Sunil, P., Prakash, J., & Megha, K. (2013) · Cited by 23
Chakraborty, S., Dlie, Z. Y., Mukherjee, B., Besra, S. E., Sengupta, S., Sen, R., & Mukherjee, A. (2020) · AAPS PharmSciTech · doi:10.1208/s12249-020-1629-z · Cited by 20
Chen, H., Sells, E., Pandey, R., Abril, E. R., Hsu, C., Krouse, R. S., Nagle, R. B., Pampalakis, G., Sotiropoulou, G., & Ignatenko, N. A. (2019) · Oncotarget · doi:10.18632/oncotarget.27153 · Cited by 17
ISG15 induction is required during L1-mediated colon cancer progression and metastasis
Cheriyamundath, S., Basu, S., Haase, G., Doernberg, H., Gavert, N. S., Brabletz, T., & Ben‐Ze'ev, A. (2019) · Oncotarget · doi:10.18632/oncotarget.27390 · Cited by 17
N-end rule pathway inhibition assists colon tumor regression via necroptosis
Agarwalla, P., & Banerjee, R. (2016) · Molecular Therapy — Oncolytics · doi:10.1038/mto.2016.20 · Cited by 15
COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW
Malleswari, K., Prasad, G. V. R., & Pavani, G. (2013) · Cited by 14
Mechanism of an ascites tumor formation.
Siegler, R. L., & Koprowska, I. (1962) · PubMed · Cited by 8
Paulson, B., Kim, I. H., Namgoong, J., Kim, Y. G., Lee, S., Moon, Y., Shin, D., Choo, M., & Kim, J. K. (2019) · International Journal of Medical Sciences · doi:10.7150/ijms.35666 · Cited by 8
A Review On: Colon Targeted Drug Delivery System
Pawar, A. M., Patil, S. R., & Fegade, T. D. (2020) · American Journal of PharmTech Research · doi:10.46624/ajptr.2020.v10.i2.016 · Cited by 8
Manikandan, M., & Kannan, K. (2017) · Journal of Applied Pharmaceutical Science · doi:10.7324/japs.2017.70303 · Cited by 7
Cited by
Sorted by citations
Xuan, L., Ju, Z., Skonieczna, M., Zhou, P., & Huang, R. (2023) · MedComm · doi:10.1002/mco2.327 · Cited by 911
Cyclodextrin nanoparticles for diagnosis and potential cancer therapy: A systematic review
Karthic, A., Roy, A., Lakkakula, J., Alghamdi, S. A., Shakoori, A. M., Babalghith, A. O., Emran, T. B., Sharma, R., Lima, C. M. G., Kim, B., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.984311 · Cited by 60
Jain, A., & Bhattacharya, S. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1211603 · Cited by 51
MiR675-5p Acts on HIF-1α to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma
Dico, A. L., Costa, V., Martelli, C., Diceglie, C., Raiata, F., Rizzo, A. G., Mancone, C., Tripodi, M., Ottobrini, L., Alessandro, R., et al. (2016) · Theranostics · doi:10.7150/thno.14700 · Cited by 51
Herbal Theranostics: Controlled, Targeted Delivery and Imaging of Herbal Molecules
Setia, A., Vallamkonda, B., Challa, R. R., Mehata, A. K., Badgujar, P., & Muthu, M. S. (2024) · Nanotheranostics · doi:10.7150/ntno.94987 · Cited by 34
Metadata
- Authors
- Ünal, S., Can Öztürk, S., Bilgiç, E., Yanık, H., Korkusuz, P., Aktaş, Y., Benito, J. M., Esendağlı, G., & Bilensoy, E.
- Affiliations
- Hacettepe University (TR)
- Erciyes University (TR)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Bilensoy, Erem
- ORCID
- Venue
- European Journal of Pharmaceutics and Biopharmaceutics
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 169
- Pages
- 168-177
- ISSN
- 0939-6411 (ISSN-L)
- OpenAlex
- W3209334983
- Cited by
- 25
- References
- 68
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 4
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- colorectal cancer, camptothecin, oral drug delivery, liver metastasis, nanoparticle drug delivery, oral bioavailability, mouse tumor model, in vivo imaging
- MeSH terms
- Polyelectrolytes, Administration, Oral, Animals, Antineoplastic Agents, Phytogenic, Biological Availability, Camptothecin, Cyclodextrins, Neoplasm Metastasis, Tissue Distribution, Colorectal Neoplasms, Drug Delivery Systems, Treatment Outcome, Models, Animal, Gastrointestinal Tract, Mice, 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
