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The Antitumor Effect of Topotecan Loaded Thiolated Chitosan-Dextran Nanoparticles for Intravitreal Chemotherapy: A Xenograft Retinoblastoma Model Publisher



Delrish E1 ; Jabbarvand M1 ; Ghassemi F1, 2 ; Amoli FA3 ; Atyabi F4, 5 ; Keshel SH6 ; Lashay A1 ; Tekie FSM4 ; Soleimani M7 ; Dinarvand R4, 5
Authors
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Authors Affiliations
  1. 1. Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Retina & Vitreous Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of pathology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: Journal of Ophthalmic and Vision Research Published:2023


Abstract

Purpose: This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model. Methods: The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested in vitro by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration. Results: NPs had a mean diameter, polydispersity index, and zeta potential of 30 ± 4 nm, 0.24 ± 0.03 and +10 ± 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, P = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 ± 2%) and vitreous seeds (89 ± 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPH-CMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection (P = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH (P > 0.05). Conclusion: This investigation revealed definitive antitumor efficacy of TPH-CMD-TCS-NPs by intravitreal administration in the rabbit xenograft retinoblastoma model. © 2023 Delrish et al.
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