Cited by 67Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsRNA Interference and Gene Delivery

Micellar delivery of dasatinib for the inhibition of pathologic cellular processes of the retinal pigment epithelium

Li, Qingqing, Lai, Ka Lun, Chan, Pui Shan, Leung, Sui Chu, Li, Ho Yin, Fang, Yuan, To, Kenneth K.W., Choi, Chung Hang J. +2 more·2016·Colloids and Surfaces B Biointerfaces

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.

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Crossref · 10.1016/j.colsurfb.2015.12.053

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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
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

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