Micellar delivery of dasatinib for the inhibition of pathologic cellular processes of the retinal pigment epithelium
Abstract
The objective of this study was to fabricate dasatinib-loaded nanoparticles and evaluate their efficacy in inhibiting cellular processes of the retinal pigment epithelium (RPE) related to proliferative vitreoretinopathy (PVR), for which there are no approved pharmacological approaches. We successfully encapsulated dasatinib, a poorly soluble multi-targeted tyrosine kinase inhibitor which has great potential for the treatment of PVR, into nanoparticles prepared from micellation of PEG-b-PCL. The size of the nanomicelles was approximately 55nm with a narrow distribution. They increased the solubility of dasatinib by 475× and provided a sustained drug release. ARPE-19, an immortal RPE cell line, was used to assess the in vitro efficacy of micellar dasatinib because the RPE is believed to play a key role in the pathogenesis of PVR. Three cell-based assays, namely, proliferation, adhesion and migration, which represent three important PVR-related cellular changes of the RPE, were conducted and the cytotoxicity of micelles was also evaluated. Both blank and dasatinib-loaded micelles were non-cytotoxic towards ARPE-19 cells. Micellar dasatinib significantly inhibited cell proliferation, adhesion and migration compared to the free drug; this might be attributable to enhanced solubility. PEG-b-PCL micelles were taken up into the ARPE-19 cells by an energy-dependent clatharin and caveolae-mediated endocytosis. Our results indicated that cellular uptake and the anti-proliferation effect of drugloaded micelles were linearly correlated. Drug loading appears to be a critical parameter for cellular uptake which in turn impacts the in vitro bioactivities of polymeric micelles. Our results clearly demonstrated that dasatinib-encapsulated micelles offer considerable promise in the management of PVR.
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?
Micellar formulations of dasatinib significantly restrained cell proliferation, adhesion, and migration compared to free dasatinib.
“Micellar formulations of dasatinib significantly restrained cell proliferation, adhesion, and migration compared to free dasatinib.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [189]
Both blank micelles and those containing dasatinib exhibited excellent safety profiles at cellular levels.
“Results indicated that both blank micelles and those containing dasatinib exhibited excellent safety profiles at cellular levels [49,189].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [189]
Dasatinib encapsulated in PEG-b-PCL micelles enhanced its solubility by 475-fold while ensuring sustained drug release.
“Li et al. successfully encapsulated dasatinib within nanoparticles derived from PEG-b-PCL micelles to enhance its solubility by 475-fold while ensuring sustained drug release.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [189]
Cites
Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells
Chithrani, D. B., Ghazani, A. A., & Chan, W. C. W. (2006) · Nano Letters · doi:10.1021/nl052396o · Cited by 4,887 · see citing works
Higuchi, T., & Connors, A. (1965) · Cited by 2,501 · see citing works
Higuchi, T. (1965) · Cited by 1,145 · see citing works
Kulkarni, S. A., & Feng, S. (2013) · Pharmaceutical Research · doi:10.1007/s11095-012-0958-3 · Cited by 771 · see citing works
Proliferative vitreoretinopathy: risk factors and pathobiology
Jimeno, J. C. P., Rodríguez-de-la-Rúa-Franch, E., & Martı́n, F. (2002) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00023-4 · Cited by 437 · see citing works
Proliferative Vitreoretinopathy
Jimeno, J. C. P. (1998) · Survey of Ophthalmology · doi:10.1016/s0039-6257(98)00023-x · Cited by 411 · see citing works
Arnida, Malugin, A., & Ghandehari, H. (2009) · Journal of Applied Toxicology · doi:10.1002/jat.1486 · Cited by 378 · see citing works
Drug delivery to the posterior segment of the eye
Thrimawithana, T. R., Young, S. A., Bunt, C. R., Green, C. R., & Alany, R. G. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.12.004 · Cited by 335 · see citing works
Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs
Shin, H.-C., Alani, A. W. G., Rao, D. A., Rockich, N. C., & Kwon, G. S. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.04.024 · Cited by 243 · see citing works
Qaddoumi, M. G., Ueda, H., Yang, J. J., et al. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000022411.47059.76 · Cited by 229 · see citing works
Zhao, L., Du, J., Duan, Y., Zang, Y.-N., Zhang, H., Yang, C., Cao, F., & Zhai, G. (2012) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2012.04.017 · Cited by 216 · see citing works
Nanomaterials for Ocular Drug Delivery
Liu, S., Jones, L., & Gu, F. (2012) · Macromolecular Bioscience · doi:10.1002/mabi.201100419 · Cited by 185 · see citing works
Forrest, M. L., Won, C.-Y., Malick, A. W., & Kwon, G. S. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.10.008 · Cited by 175 · see citing works
The retinal pigment epithelium: An important player of retinal disorders and regeneration
Chiba, C. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.07.009 · Cited by 172 · see citing works
Aliabadi, H. M., Elhasi, S., Mahmud, A., GULAMHUSEIN, R., Mahdipoor, P., & Lavasanifar, A. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.08.018 · Cited by 172 · see citing works
Suen, W.-L. L., & Chau, Y. (2013) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12134 · Cited by 161 · see citing works
Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy?
Pennock, S., Haddock, L. J., Eliott, D., Mukai, S., & Kazlauskas, A. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2013.12.006 · Cited by 158 · see citing works
Review: Practical Issues in Intravitreal Drug Delivery
Maurice, D. M. (2001) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/108076801753162807 · Cited by 150 · see citing works
Yasin, M. N., Svirskis, D. M., Seyfoddin, A., & Rupenthal, I. D. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.09.030 · Cited by 146 · see citing works
Choonara, Y. E., Pillay, V., Danckwerts, M. P., Carmichael, T. R., & du Toit, L. C. (2009) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21987 · Cited by 139 · see citing works
Diclofenac/biodegradable polymer micelles for ocular applications
Li, X., Zhang, Z., Li, J., Sun, S., Weng, Y., & Chen, H. (2012) · Nanoscale · doi:10.1039/c2nr30924f · Cited by 126 · see citing works
Cho, H., Lai, T. C., & Kwon, G. S. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.12.005 · Cited by 112 · see citing works
Promotion of adhesion and migration of RPE cells to provisional extracellular matrices by TNF-alpha.
Jin, M., He, S., Woerpel, V., Ryan, S. J., & Hinton, D. R. (2000) · PubMed · Cited by 103 · see citing works
Lei, H., & Kazlauskas, A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808426200 · Cited by 102 · see citing works
Lei, H., Rhéaume, M., & Kazlauskas, A. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.11.003 · Cited by 98 · see citing works
Ikuno, Y., Leong, F., & Kazlauskas, A. (2000) · PubMed · Cited by 69 · see citing works
Suen, W.-L. L., & Chau, Y. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.01.004 · Cited by 68 · see citing works
A facile surfactant critical micelle concentration determination
Cai, L., Gochin, M., & Liu, K. (2011) · Chemical Communications · doi:10.1039/c1cc10605h · Cited by 68 · see citing works
Lee, T. W.-Y., & Robinson, J. R. (2001) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/10807680152729257 · Cited by 66 · see citing works
Self-citationA Novel Strategy to Develop Therapeutic Approaches to Prevent Proliferative Vitreoretinopathy
Pennock, S., Rhéaume, M., Mukai, S., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.08.043 · Cited by 64 · see citing works
Intravitreal drug delivery in retinal disease: are we out of our depth?
Thakur, S. S., Barnett, N., Donaldson, M., & Parekh, H. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.927864 · Cited by 61 · see citing works
Ikuno, Y., & Kazlauskas, A. (2002) · PubMed · Cited by 59 · see citing works
Pennock, S., & Kazlauskas, A. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06668-11 · Cited by 55 · see citing works
Szurman, P., Kaczmarek, R. T., Spitzer, M. S., et al. (2006) · Experimental Eye Research · doi:10.1016/j.exer.2006.02.012 · Cited by 53 · see citing works
Inhibition of PVR with a Tyrosine Kinase Inhibitor, Dasatinib, in the Swine
Umazume, K., Liu, L., Scott, P. A., de Castro, J. P. F., McDonald, K., Kaplan, H. J., & Tamiya, S. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10418 · Cited by 51 · see citing works
Drug delivery techniques for treating age-related macular degeneration
Schwartz, S. G., Scott, I. U., Flynn, H. W., & Stewart, M. W. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.859135 · Cited by 49 · see citing works
Man, D. K.-W., Casettari, L., Cespi, M., Bonacucina, G., Palmieri, G. F., Sze, S. C. W., Leung, G., Lam, J. K. W., & Kwok, P. C. L. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00085 · Cited by 49 · see citing works
Lei, H., & Kazlauskas, A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00839-13 · Cited by 48 · see citing works
Effect of Growth Factors on Bovine Retinal Pigment Epithelial Cell Migration and Proliferation
Spraul, C. W., Kaven, C., Lang, G. K., & Lang, G. E. (2004) · Ophthalmic Research · doi:10.1159/000077330 · Cited by 46 · see citing works
Ocular biocompatibility and tolerance study of biodegradable polymeric micelles in the rabbit eye
Xu, L., Xu, X., Chen, H., & Li, X. (2013) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2013.06.047 · Cited by 45 · see citing works
Shen, J., Durairaj, C., Lin, T., Liu, Y., & Burke, J. A. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13650 · Cited by 39 · see citing works
Saxena, V., & Hussain, M. D. (2013) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2013.07.031 · Cited by 33 · see citing works
Eibl, K. H. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0657 · Cited by 26 · see citing works
Wang, Y., Gou, M., Gong, C., Wang, C., Qian, Z., Lin, Y., & Luo, F. (2012) · Current Drug Metabolism · doi:10.2174/138920012800166490 · Cited by 25 · see citing works
Zhao, Z., Wang, Y., Han, J., Wang, K., Yang, D., Yang, Y., Du, Q., Song, Y., & Yin, X. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s73111 · Cited by 25 · see citing works
Lee, T. W.-Y., & Robinson, J. R. (2009) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2008.0010 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mandal, A., Bisht, R., Rupenthal, I. D., & Mitra, A. K. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.01.012 · Cited by 481 · see citing works
Polymeric micelles of biodegradable diblock copolymers: enhanced encapsulation of hydrophobic drugs
Hussein, Y. H. A., & Youssry, M. (2018) · Materials · doi:10.3390/ma11050688 · Cited by 196 · see citing works
Nanoparticulate drug delivery to the retina
Li, Q., Weng, J., Wong, S. N., Thomas Lee, W. Y., & Chow, S. F. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00224 · Cited by 59 · see citing works
Self-citationLi, Q., Qian, X., Li, H. Y., Lai, K. L., Gao, Q., & Lee, W. Y. T. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120226 · Cited by 26 · see citing works
Self-citationFrom design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics
Sun, M., Wang, J., Fan, W., Wang, K., Wang, Y., Zhang, J., Ding, S., Zhang, C., Feng, Z., Wang, Y.-G., et al. (2025) · Materials today. Bio · doi:10.1016/j.mtbio.2025.102537 · Cited by 7 · see citing works
“Results indicated that both blank micelles and those containing dasatinib exhibited excellent safety profiles at cellular levels [49,189].”
- Authors
- Li, Q., Lai, K. L., Chan, P. S., Leung, S. C., Li, H. Y., Fang, Y., To, K. K. W., Choi, C. H. J., Gao, Q. Y., & Lee, T. W. Y.
- Affiliations
- Chinese University of Hong Kong (HK)
- Sun Yat-sen University (CN)
- Corresponding author
- Lee, Thomas W.Y.
- Venue
- Colloids and Surfaces B Biointerfaces
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 140
- Pages
- 278-286
- ISSN
- 0927-7765 (ISSN-L)
- OpenAlex
- W2242638709
- Cited by
- 67
- References
- 46
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 9
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Colloids and Surfaces B Biointerfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese University of Hong Kong
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- dasatinib, micellar drug delivery, polymeric micelles, PEG-b-PCL, retinal pigment epithelium, proliferative vitreoretinopathy, ARPE-19 cells, drug solubility enhancement, sustained drug release, cell proliferation inhibition, cell adhesion, cell migration, endocytosis, drug loading, tyrosine kinase inhibitors
- MeSH terms
- Dasatinib, Cell Adhesion, Cell Line, Cell Movement, Cell Survival, Humans, Micelles, Microscopy, Fluorescence, Particle Size, Vitreoretinopathy, Proliferative, Protein Kinase Inhibitors, Cell Proliferation, Nanoparticles, Retinal Pigment Epithelium, 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