Efficacy of topotecan nanoparticles for intravitreal chemotherapy of retinoblastoma.

Autor: Delrish E; Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran., Jabbarvand M; Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran., Ghassemi F; Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran; Retina & Vitreous Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran., Amoli FA; Department of Pathology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran., Atyabi F; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Lashay A; Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran., Soleimani M; Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Aghajanpour L; Stem Cell Preparation Unit, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran., Dinarvand R; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dinarvand@tums.ac.ir.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2021 Mar; Vol. 204, pp. 108423. Date of Electronic Publication: 2021 Jan 13.
DOI: 10.1016/j.exer.2020.108423
Abstrakt: Retinoblastoma (Rb) is the most common intraocular malignancy in children that accounts for approximately 4% of all pediatric malignancies. Since chemotherapy is a widely practiced treatment for Rb, there is a growing interest in developing new and effective drugs to overcome systemic and local side effects of chemotherapy to improve the quality of life and increase the chances of survival. This study sought to fabricate thiolated chitosan nanoparticles containing topotecan (TPH-TCs-NPs) with a view of enhancing drug loading and release control. This research was also designed to assess the ability of TPH-TCs-NPs to improve cell association, increase treatment efficacy in retinoblastoma cells and xenograft-rat-model of retinoblastoma, and overcome current topotecan hydrochloride (TPH) intravitreal administration challenges, including stability loss and poor cellular uptake. Modified ionic gelation method was optimized to fabricate TPH-TCs-NPs and TPH-TMC-NPs (N-trimethyl chitosan nanoparticles containing TPH). We characterized the NPs and quantified topotecan loading and release against a free TPH standard. The efficacy of TPH-NPs was quantified in human retinoblastoma cells (Y79) by XTT and flow cytometry measurement. In addition, Y79 cells were injected intravitreally in both eyes of immunodeficient wistar albino rats to create a xenograft-rat-model to compare the antitumor effectiveness of TPH-NPs and TPH by intravitreal administration. TPH-NPs complexation was confirmed by EDX, FTIR, and DSC techniques. TPH-TCs-NPs and TPH-TMC-NPs had high encapsulation efficiency (85.23 ± 2 and 73.34 ± 2% respectively). TPH-TCs-NPs showed a mean diameter, polidispersity index, and zeta potential of 25±2 nm, 0.21 ± 0.03 and +12 ± 2 mV, respectively. As a function of dose, TCs and TMC NPs were more efficacious than free topotecan (IC50s 53.17 and 85.88 nM, relative to 138.30 nM respectively, P = 0.012). Kruskal-Wallis test showed a statistically significant difference between the groups. Additionally, a significant difference between the tumor control and TPH-TCs-NPs treated group in xenograft-rat-model ( Range of P-value: 0.026 to 0.035) was shown by Bonferroni post hoc test. The current investigation demonstrated enhanced efficacy and association of TPH-TCs-NPs relative to free TPH in retinoblastoma cells and tumor in vitro and in vivo.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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