Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes
Open accessAbstract
The aim of this work was to clarify the dynamics behind the influence of ionic strength on the changes in drug release from large unilamellar vesicles (LUVs). For this purpose, we have investigated the transport of two different model drugs (caffeine and hydrocortisone) formulated into liposomes through different types of barriers with different retention properties (regenerated cellulose and the newly introduced biomimetic barrier, Permeapad®). Drug release from liposomes was studied utilizing the standard Franz diffusion cells. LUV dispersions were exposed to the isotonic, hypotonic and hypertonic environment (difference of 300 mOsm/kg between the initial LUVs and the environment) and experimental data treated with both linear and non-linear (Korsmeyer-Peppas) regression models. To alter the rigidity of the liposomal membranes, cholesterol was introduced in the liposomal barriers (up to 25% w/w). Korsmeyer-Peppas model was proven to be suited to analyse experimental data throughout the experimental time frame, providing important additive information in comparison to standard linear approximation. The obtained results are highly relevant as they improve the interpretation of drug release kinetics from LUVs under osmotic stress. Moreover, the findings can be utilized in the development of liposomal formulations intended for nose-to-brain targeted drug delivery.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
At pH 3.0, aNFC release was diffusion-driven and relatively fast.
“indicating a diffusion-driven and relatively fast release [53].”
From Amidated Pectin/Nanocellulose Hybrid Cryogel System with a pH-Responsive Release Profile for Small Intestinal Delivery (2025) · cites this paper as [53]
At pH 3.0, aNFC exhibited n ≈ 0.40, close to the Fickian diffusion threshold, and a relatively high k.
“At pH 3.0, aNFC exhibited n ≈ 0.40, close to the Fickian diffusion threshold, and a relatively high k, indicating a diffusion-driven and relatively fast release [53].”
From Amidated Pectin/Nanocellulose Hybrid Cryogel System with a pH-Responsive Release Profile for Small Intestinal Delivery (2025) · cites this paper as [53]
Cites
Modeling and comparison of dissolution profiles
Costa, P., & Sousa Lobo, J. M. (2001) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(01)00095-1 · Cited by 5,509 · see citing works
Liposomal drug delivery systems: From concept to clinical applications
Allen, T. M., & Cullis, P. R. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.037 · Cited by 4,839 · see citing works
Bangham, A. D., & Horne, R. W. (1964) · Journal of Molecular Biology · doi:10.1016/s0022-2836(64)80115-7 · Cited by 1,810 · see citing works
Influence of cholesterol on liposome stability and on in vitro drug release
Briuglia, M. L., Rotella, C., McFarlane, A., et al. (2015) · Drug Delivery and Translational Research · doi:10.1007/s13346-015-0220-8 · Cited by 745 · see citing works
Paula, S., Volkov, A. G., Van Hoek, A. N., Haines, T. H., & Deamer, D. W. (1996) · Biophysical Journal · doi:10.1016/s0006-3495(96)79575-9 · Cited by 578 · see citing works
Composition design and medical application of liposomes
Li, M., Du, C., Guo, N., Teng, Y., Meng, X., Sun, H., Li, S., Yu, P., & Galons, H. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.01.007 · Cited by 561 · see citing works
Osmotic properties and water permeability of phospholipid liquid crystals
Bangham, A. D., de Gier, J., & Greville, G. D. (1967) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(67)90030-8 · Cited by 546 · see citing works
Vieira, D., & Gamarra, L. (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s117210 · Cited by 427 · see citing works
Chemical stability of liposomes: implications for their physical stability
Grit, M., & Crommelin, D. J. A. (1993) · Chemistry and Physics of Lipids · doi:10.1016/0009-3084(93)90053-6 · Cited by 405 · see citing works
Mohammed, A. R., Weston, N. J., Coombes, A. G. A., et al. (2004) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2004.07.010 · Cited by 388 · see citing works
In vitro release kinetics model fitting of liposomes: An insight
Jain, A., & Jain, S. (2016) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2016.10.005 · Cited by 374 · see citing works
Wiley Encyclopedia of Chemical Biology
Begley, T. P. (2008) · Wiley eBooks · doi:10.1002/9780470048672 · Cited by 365 · see citing works
Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics
Bourganis, V., Kammona, O., Alexopoulos, A., & Kiparissides, C. (2018) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2018.05.009 · Cited by 357 · see citing works
Zhu, C., Jiang, L., Chen, T., & Hwang, K. (2002) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(02)01360-0 · Cited by 352 · see citing works
Nanoparticulate Systems for Nasal Delivery of Drugs: A Real Improvement over Simple Systems?
Illum, L. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20718 · Cited by 238 · see citing works
Osmotic properties of large unilamellar vesicles prepared by extrusion
Mui, B. L., Cullis, P. R., Evans, E. A., & Madden, T. D. (1993) · Biophysical Journal · doi:10.1016/s0006-3495(93)81385-7 · Cited by 220 · see citing works
Flaten, G. E., Dhanikula, A. B., Luthman, K., & Brandl, M. (2005) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.08.007 · Cited by 180 · see citing works
A study of rivastigmine liposomes for delivery into the brain through intranasal route
Arumugam, K., Subramanian, G., Mallayasamy, S., Averineni, R. K., Reddy, M. S., & Udupa, N. (2008) · Acta Pharmaceutica · doi:10.2478/v10007-008-0014-3 · Cited by 162 · see citing works
The effect of feed ionic strength on salt passage through reverse osmosis membranes
Bartels, C. R., Franks, R., Rybar, S., Schierach, M. K., & Wilf, M. (2005) · Desalination · doi:10.1016/j.desal.2005.04.032 · Cited by 152 · see citing works
New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs
di Cagno, M., Bibi, H. A., & Bauer-Brandl, A. (2015) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2015.03.019 · Cited by 146 · see citing works
Self-citationThe rheology of nasal mucus: a review
Quraishi, M. S., Jones, N. S., & Mason, J. (1998) · Clinical Otolaryngology · doi:10.1046/j.1365-2273.1998.00172.x · Cited by 129 · see citing works
Lai, F., Fadda, A. M., & Sinico, C. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.766714 · Cited by 118 · see citing works
Osmotically Induced Shape Changes of Large Unilamellar Vesicles Measured by Dynamic Light Scattering
Pencer, J., White, G. F., & Hallett, F. R. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)75914-0 · Cited by 114 · see citing works
Solomon, D., Gupta, N., Mulla, N. S., Shukla, S. K., Guerrero, Y. A., & Gupta, V. (2017) · The AAPS Journal · doi:10.1208/s12248-017-0142-0 · Cited by 104 · see citing works
Haghiralsadat, F., Amoabediny, G., Helder, M. N., Naderinezhad, S., Sheikhha, M. H., Forouzanfar, T., & Zandieh‐Doulabi, B. (2017) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2017.1304403 · Cited by 101 · see citing works
Experimental Estimation of Membrane Tension Induced by Osmotic Pressure
Shibly, S. U. A., Ghatak, C., Karal, M. A. S., et al. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.09.043 · Cited by 96 · see citing works
How to measure release from nanosized carriers?
Nothnagel, L., & Wacker, M. G. (2018) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2018.05.004 · Cited by 73 · see citing works
The effect of hypertonicity on nasal mucociliary clearance
Homer, J. J., Dowley, A., Condon, L. T., Jassar, P., & Sood, S. (2000) · Clinical Otolaryngology · doi:10.1046/j.1365-2273.2000.00420.x · Cited by 69 · see citing works
Ali, M. H., Kirby, D. J., Mohammed, A. R., et al. (2010) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.2010.01090.x · Cited by 63 · see citing works
Milon, A., Lazrak, T., Albrecht‐Gary, A., Wolff, G., Weill, G., Ourisson, G., & Nakatani, Y. (1986) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(86)90311-1 · Cited by 59 · see citing works
Dynamic Behavior of Giant Liposomes at Desired Osmotic Pressures
Ohno, M., Hamada, T., Takiguchi, K., & Homma, M. (2009) · Langmuir · doi:10.1021/la900777g · Cited by 59 · see citing works
Ohwaki, T., Ando, H., Kakimoto, F., et al. (1987) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600760905 · Cited by 58 · see citing works
Xie, Y., Shao, N., Jin, Y., et al. (2017) · Journal of Chromatography B · doi:10.1016/j.jchromb.2017.11.020 · Cited by 57 · see citing works
Polozov, I. V., Anantharamaiah, G. M., Segrest, J. P., & Epand, R. M. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)75753-0 · Cited by 53 · see citing works
Sun, S.-T., Milon, A., Tanaka, T., et al. (1986) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(86)90549-3 · Cited by 44 · see citing works
di Cagno, M. P., & Luppi, B. (2013) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.01.006 · Cited by 43 · see citing works
Fujiwara, K., & Yanagisawa, M. (2014) · ACS Synthetic Biology · doi:10.1021/sb4001917 · Cited by 40 · see citing works
Cholesterol modulates curcumin partitioning and membrane effects
Leite, N. B., Martins, D. B., Fazani, V. E., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.05.018 · Cited by 40 · see citing works
Development of a Flow-Through USP-4 Apparatus Drug Release Assay to Evaluate Doxorubicin Liposomes
Yuan, W., Kuai, R., Dai, Z., Yuan, Y., Zheng, N., Jiang, W., Noble, C. O., Hayes, M. E., Szoka, F. C., & Schwendeman, A. A. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9958-2 · Cited by 39 · see citing works
Tang, J., Srinivasan, S., Yuan, W., Ming, R., Liu, Y., Dai, Z., Noble, C. O., Hayes, M. E., Zheng, N., Jiang, W., et al. (2018) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2018.11.010 · Cited by 39 · see citing works
Pedersen, P. S., Braunstein, T. H., Jørgensen, A., et al. (2006) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-006-0157-3 · Cited by 26 · see citing works
di Cagno, M. P., & Stein, P. C. (2019) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2019.04.005 · Cited by 19 · see citing works
Passive Diffusion Across Membranes
Brandl, M., Flaten, G. E., & Bauer‐Brandl, A. (2008) · Wiley Encyclopedia of Chemical Biology · doi:10.1002/9780470048672.wecb432 · Cited by 16 · see citing works
Wu, I. Y., Nikolaisen, T. E., Škalko‐Basnet, N., & di Cagno, M. P. (2019) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2019.03.006 · Cited by 16 · see citing works
Self-citationPhospholipid-detergent systems: effects of polysorbates on the release of liposomal caffeine
Fadda, A. M., Baroli, B. M., Maccioni, A. M., et al. (1998) · Il Farmaco · doi:10.1016/s0014-827x(98)00081-0 · Cited by 15 · see citing works
A Study of Membrane Potentials Across a Cellophane Membrane for Different Electrolytes
Benavente, J. (1984) · Journal of Non-Equilibrium Thermodynamics · doi:10.1515/jnet.1984.9.3.217 · Cited by 13 · see citing works
Wu, I. Y., Škalko‐Basnet, N., & di Cagno, M. P. (2017) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2017.05.062 · Cited by 11 · see citing works
Self-citationChallenges in the drug release testing of next-generation nanomedicines – What do we know?
Wacker, M. G. (2017) · Materials Today Proceedings · doi:10.1016/j.matpr.2017.09.189 · Cited by 9 · see citing works
Response of unilamellar DPPC and DPPC:SM vesicles to hypo and hyper osmotic shocks: A comparison
Ahumada, M., Calderón, C., Álvarez, C., Lanio, M. E., & Lissi, E. A. (2015) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2015.05.001 · Cited by 8 · see citing works
Permeability of iodide in multilamellar liposomes modeled by two compartments and a reservoir
Schullery, S. E. (1977) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(77)90117-1 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Drug Permeability Profiling Using the Novel Permeapad® 96-Well Plate
Jacobsen, A.-C., Nielsen, S., Brandl, M., & Bauer-Brandl, A. (2020) · Pharmaceutical Research · doi:10.1007/s11095-020-02807-x · Cited by 55 · see citing works
Feng, S., Laurén, P., Zini, J., Gounani, Z., Bi, J., Yi, J., & Laaksonen, T. (2025) · Gels · doi:10.3390/gels11090700 · Cited by 5 · see citing works
“At pH 3.0, aNFC exhibited n ≈ 0.40, close to the Fickian diffusion threshold, and a relatively high k , indicating a diffusion-driven and relatively fast release [53].”
Influential
- Authors
- Wu, I. Y., Bala, S., Škalko-Basnet, N., & di Cagno, M. P.
- Affiliations
- UiT The Arctic University of Norway (NO)
- Venue
- European Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 138
- Pages
- 105026
- ISSN
- 0928-0987 (ISSN-L)
- OpenAlex
- W2966544855
- Cited by
- 439
- References
- 50
- Citations by year
- 2026: 90 · 2025: 107 · 2024: 78 · 2023: 63 · 2022: 47 · 2021: 31 · 2020: 22 · 2019: 1
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- European Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- Funders
- University of Tromsø - The Arctic University of Norway
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- liposomes, drug release kinetics, Korsmeyer-Peppas model, large unilamellar vesicles, ionic strength, osmotic stress, caffeine, cortisol, cholesterol, membrane rigidity, nose-to-brain delivery, Franz diffusion cell
- MeSH terms
- Cholesterol, Diffusion, Pharmaceutical Preparations, Kinetics, Liposomes, Membranes, Drug Delivery Systems, Drug Liberation
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