Journal
MATERIALS TODAY NANO
Volume 20, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.mtnano.2022.100264
Keywords
Ocular drug delivery; Neovascular ocular diseases; Sunitinib; Acriflavine; Minimally-invasive treatment
Funding
- National Science and Technology Major Special Project -Major New Drug Creation
- National Natural Science Foundation of China
- Shandong Provincial Program of Taishan Industrial Experts
- Natural Science Foundation of Shandong Province, P.R. China
- China Postdoctoral Science Foundation
- [2019ZX09301- 112]
- [32000929]
- [82104094]
- [ZR2020QH196]
- [ZR2020QH351]
- [2021M700083]
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Choroidal neovascularization (CNV) is a common cause of severe vision loss in the elderly. The current treatment method of intravitreal injection of anti-VEGF drug has limitations. In this study, a novel liposome-loaded injectable hydrogel was developed for the treatment of CNV using a minimally invasive sub-tenon's injection. The results showed strong anti-angiogenesis effect and enhanced anti-CNV effect of the drug delivery system, providing a new minimally invasive alternative for neovascular ocular diseases.
As a common multifactor fundus lesion, choroidal neovascularization (CNV) has become the leading cause of severe vision loss in the elderly. The mainstay treatment is an invasive intravitreal injection of anti-VEGF drug, which leads to a short half-life, incomplete response, and severe ocular complications. In this work, we have developed a novel, liposome-loaded, injectable hydrogel (cSA@Lip-HAC) by a mini-mally invasive sub-tenon's injection for CNV treatment. First, the multitarget angiogenic inhibitor (sunitinib) and hypoxia-inducible factor inhibitor (acriflavine) were co-loaded in the liposome, which was then loaded in the injectable hydrogel. The in vitro results showed that the cSA@Lip-HAC group had a strong anti-angiogenesis effect. After sub-tenon's injection, the hydrogel endowed the drug-loaded liposome with a longer retention time in the target area. In the CNV model, cSA@Lip-HAC showed a significant anti-CNV effect, which was superior to that of intravitreal injection of a commercial product (Conbercept). Exploration of the molecular mechanism revealed that cSA@Lip-HAC did not only inhibit CNV through the AKT/mTOR/HIF-1a/VEGF signal pathways but also inhibit VEGF R1 and VEGF R2. In conclusion, this novel drug delivery system, combining the merits of the liposome and hydrogel, showed an enhanced anti-CNV effect, thus providing a new and minimally invasive alternative for the treatment of neovascular ocular diseases.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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