Is dialysis a reliable method for studying drug release from nanoparticulate systems?—A case study
Abstract
The kinetics of in vitro drug release from nanoparticulate systems is extensive, though uncritically, being studied by dialysis. Evaluating the actual relevance of dialysis data to drug release was the purpose of this study. Diclofenac- or ofloxacin-loaded chitosan nanoparticles crosslinked with tripolyphosphate were prepared and characterized. With each drug, dynamic dialysis was applied to nanoparticle dispersion, solution containing dissolved chitosan·HCl, and solution of plain drug. Drug kinetics in receiving phase (KRP), nanoparticle matrix (KNM) and nanoparticle dispersion medium (KDM) were determined. Release of each drug from nanoparticles was also assessed by ultracentrifugation. Although KRP data may be interpreted in terms of sustained release from nanoparticles, KNM and KDM data show that, with both drugs, the process was in fact controlled by permeation across dialysis membrane. Analysis of KRP data reveals a reversible interaction of diclofenac with dispersed nanoparticle surface, similar to the interaction of this drug with dissolved chitosan·HCl. No such interactions are noticed with ofloxacin. The results from the ultracentrifugation method agree with the above interpretation of dialysis data. This case study shows that dialysis data from a nanoparticle dispersion is not necessarily descriptive of sustained-release from nanoparticles, hence, if interpreted uncritically, it may be misleading.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles
Keawchaoon, L., & Yoksan, R. (2011) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2010.12.031 · Cited by 660 · see citing works
Mass transport Phenomena and Models: Theoretical Concepts
Flynn, G. L., Yalkowsky, S. H., & Roseman, T. J. (1974) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600630403 · Cited by 515 · see citing works
Seju, U., Kumar, A., & Sawant, K. K. (2011) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.07.025 · Cited by 367 · see citing works
Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin
Kakkar, V., Singh, S., Singla, D., & Kaur, I. P. (2010) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201000310 · Cited by 352 · see citing works
Effects of Tween 20® and Tween 80® on the Stability of Albutropin During Agitation
Chou, D. K., Krishnamurthy, R., Randolph, T. W., et al. (2005) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20365 · Cited by 309 · see citing works
Peng, X., & Fang, F. F. F. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s17386 · Cited by 268 · see citing works
Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting
Alex, M. R. A., Chacko, A. J., Jose, S., & Souto, E. B. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.10.002 · Cited by 259 · see citing works
Thomas, C., Rawat, A. K., Hope‐Weeks, L. J., & Ahsan, F. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100255c · Cited by 241 · see citing works
Wang, Y., Guo, R., Cao, X., et al. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2010.12.060 · Cited by 190 · see citing works
Lin, X., Tian, Wei, Feng, Huang, Wang, Ren, R., & Diao (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s16570 · Cited by 189 · see citing works
Ji, J., Hao, S., Weiqi, L., Wu, D., Tengfei, W., & Xu, Y. (2010) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2010.11.005 · Cited by 162 · see citing works
Sanna, V., Roggio, A. M., Posadino, A. M., Cossu, A., Marceddu, S., Mariani, A., Alzari, V., Uzzau, S., Pintus, G., & Sechi, M. (2011) · Nanoscale Research Letters · doi:10.1186/1556-276x-6-260 · Cited by 157 · see citing works
Kumar, G. V., Nair, L., Jagadeeshan, S., & Nair, S. A. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s20165 · Cited by 142 · see citing works
Sandri, G., Bonferoni, M. C., Rossi, S., et al. (2006) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.07.016 · Cited by 141 · see citing works
Atyabi, F., Saremi, S., Akhlaghi, S. P., Dinarvand, R., & Ostad, S. N. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s15500 · Cited by 132 · see citing works
Diclofenac Solubility: Independent Determination of the Intrinsic Solubility of Three Crystal Forms
Llinàs, A., Burley, J., Box, K. J., Glen, R. C., & Goodman, J. M. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0612970 · Cited by 131 · see citing works
Paul, S. D., & Suresh, P. K. (2010) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2010.07.003 · Cited by 129 · see citing works
Kumari, A., Yadav, S. K., Pakade, Y. B., Kumar, V., Singh, B., Chaudhary, A., & Yadav, S. C. (2010) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2010.08.046 · Cited by 124 · see citing works
Saboktakin, M. R., Tabatabaie, R. M., Maharramov, A. M., et al. (2010) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2010.10.005 · Cited by 117 · see citing works
Performance evaluation of PAMAM dendrimer based simvastatin formulations
Kulhari, H., Pooja, D., Prajapati, S. K., & Chauhan, A. S. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.12.002 · Cited by 113 · see citing works
Song, N., Liu, W., Tu, Q., Liu, R., Zhang, Y., & Wang, J. (2011) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2011.06.009 · Cited by 109 · see citing works
Novel protein-loaded chondroitin sulfate–chitosan nanoparticles: Preparation and characterization
Yeh, M., Cheng, K., Hu, C.-S., et al. (2011) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.06.026 · Cited by 108 · see citing works
Development of Lipid-Based Nanoparticles for Enhancing the Oral Bioavailability of Paclitaxel
Pandita, D., Ahuja, A., Lather, V., Benjamin, B., Dutta, T., Velpandian, T., & Khar, R. K. (2011) · AAPS PharmSciTech · doi:10.1208/s12249-011-9636-8 · Cited by 104 · see citing works
Nagarwal, R. C., Singh, P. N., Kant, S., et al. (2011) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.59.272 · Cited by 104 · see citing works
Gupta, N. K., Tomar, P., Sharma, V., & Dixit, V. K. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.09.033 · Cited by 97 · see citing works
Washington, C. (1989) · International Journal of Pharmaceutics · doi:10.1016/0378-5173(89)90062-8 · Cited by 95 · see citing works
Essa, S., Rabanel, J., & Hildgen, P. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.02.039 · Cited by 94 · see citing works
Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles
Fan, J., Fang, G., Wang, X., et al. (2011) · Nanotechnology · doi:10.1088/0957-4484/22/45/455102 · Cited by 92 · see citing works
Folate-functionalized nanoparticles for controlled 5-Fluorouracil delivery
Zhang, Y., Li, J., Lang, M., et al. (2010) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2010.10.054 · Cited by 76 · see citing works
Zhou, W., Zhao, M., Yuan, Z. K., et al. (2011) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-011-4304-9 · Cited by 65 · see citing works
Thamake, S. I., Raut, S., Ranjan, A. P., Gryczynski, Z. K., & Vishwanatha, J. K. (2010) · Nanotechnology · doi:10.1088/0957-4484/22/3/035101 · Cited by 64 · see citing works
Lactoferrin-Conjugated Dendritic Nanoconstructs for Lung Targeting of Methotrexate
Kurmi, B. D., Gajbhiye, V., Kayat, J., & Jain, N. K. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22469 · Cited by 61 · see citing works
Tan, Y., & Liu, C. (2011) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-011-4302-y · Cited by 60 · see citing works
Saboktakin, M. R., Tabatabaie, R. M., Maharramov, A. M., et al. (2011) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2011.07.006 · Cited by 58 · see citing works
Plasma Protein Binding of Gyrase Inhibitors
Zlotos, G., Bucker, A., Kinzig‐Schippers, M., et al. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js970181b · Cited by 57 · see citing works
Pathan, S. A., Jain, G. K., Zaidi, S. M. A., et al. (2010) · Biomedical Chromatography · doi:10.1002/bmc.1492 · Cited by 56 · see citing works
Mahjub, R., Dorkoosh, F. A., Amini, M., Khoshayand, M. R., & Rafiee‐Tehrani, M. (2011) · AAPS PharmSciTech · doi:10.1208/s12249-011-9716-9 · Cited by 55 · see citing works
Carbohydrate modified ultrafine ceramic nanoparticles for allergen immunotherapy
Pandey, R. S., Sahu, S., Sudheesh, M. S., Madan, J., Kumar, M., & Dixit, V. K. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.02.004 · Cited by 47 · see citing works
Zambito, Y., Zaino, C., Uccello‐Barretta, G., Balzano, F., & Colo, G. D. (2008) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2008.01.004 · Cited by 47 · see citing works
Self-citationSahu, S. K., Maiti, S., Maiti, T. K., Ghosh, S. K., & Pramanik, P. (2010) · Macromolecular Bioscience · doi:10.1002/mabi.201000353 · Cited by 44 · see citing works
Das, S., Jagan, L., Isiah, R., et al. (2011) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.83111 · Cited by 43 · see citing works
Jain, R. D., Dandekar, P. P., Loretz, B., et al. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.08.030 · Cited by 40 · see citing works
Synthesis and antitumor efficacy of daunorubicin-loaded magnetic nanoparticles
Chen, B., Wang, J., Chen, B., et al. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s16165 · Cited by 40 · see citing works
Khazaeinia, T., & Jamali, F. (2004) · PubMed · Cited by 39 · see citing works
Zhang, C.-L., & Wang, Y. (2008) · Journal of Chemical & Engineering Data · doi:10.1021/je7007044 · Cited by 34 · see citing works
Evaluation of a Dynamic Permeation Technique for Studying Drug–Macromolecule Interactions
Bottari, F., Colo, G. D., Nannipieri, E., et al. (1975) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600640610 · Cited by 33 · see citing works
Hydroxypropyl-β-Cyclodextrin Copolymers and Their Nanoparticles as Doxorubicin Delivery System
Wang, T., Zhang, C., Liang, X., Liang, W. P., & Wu, Y. F. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22352 · Cited by 28 · see citing works
Xu, X., Wang, Y., Chen, R.-Y., et al. (2011) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.59.260 · Cited by 26 · see citing works
Benvenga, M. J., Overshiner, C. D., Monn, J. A., & Leander, J. D. (1999) · Drug Development Research · doi:10.1002/(sici)1098-2299(199905)47:1 · Cited by 16 · see citing works
Panchamukhi, S. I., Mulla, J. A. S., Shetty, N. S., et al. (2011) · Archiv der Pharmazie · doi:10.1002/ardp.201000227 · Cited by 11 · see citing works
Wu, Y. F., Fang, J., Han, S., et al. (2011) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2011.04.010 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ghezzi, M., Pescina, S., Padula, C., Santi, P., Del Favero, E., Cantù, L., & Nicoli, S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.02.031 · Cited by 1,135 · see citing works
Drug release study of the chitosan-based nanoparticles
Herdiana, Y., Wathoni, N., Shamsuddin, S., & Muchtaridi, M. (2022) · Heliyon · doi:10.1016/j.heliyon.2021.e08674 · Cited by 576 · see citing works
Predicting drug release kinetics from nanocarriers inside dialysis bags
Yu, M., Yuan, W., Li, D., Schwendeman, A., & Schwendeman, S. P. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.09.016 · Cited by 232 · see citing works
- Authors
- Zambito, Y., Pedreschi, E., & Di Colo, G.
- Affiliations
- University of Pisa (IT)
- Corresponding author
- Zambito, Y.
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 434
- Issue
- 1-2
- Pages
- 28-34
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2037818300
- Cited by
- 136
- References
- 51
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 9 · 2023: 12 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 11 · 2018: 8 · 2017: 10 · 2016: 14 · 2015: 9 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- University of Pisa
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- dialysis, drug release kinetics, chitosan nanoparticles, sodium tripolyphosphate crosslinking, diclofenac, ofloxacin, drug-nanoparticle interaction, sustained drug release, ultracentrifugation, nanoparticle dispersion
- MeSH terms
- Chemistry, Pharmaceutical, Cross-Linking Reagents, Delayed-Action Preparations, Dialysis, Diclofenac, Drug Carriers, Kinetics, Polyphosphates, Technology, Pharmaceutical, Ultracentrifugation, Reproducibility of Results, Ofloxacin, Chitosan, 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