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

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. inaddition, 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 126.20nm, 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 tphcmd-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-tcsnps by intravitreal administration in the rabbit xenograft retinoblastoma model.