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Cy5标记的巯基化和甲基化壳聚糖-羧甲基葡聚糖纳米颗粒在视网膜母细胞瘤动物模型中的生物分布

Biodistribution of Cy5-labeled Thiolated and Methylated Chitosan-Carboxymethyl Dextran Nanoparticles in an Animal Model of Retinoblastoma.

作者信息

Delrish Elham, Ghassemi Fariba, Jabbarvand Mahmoud, Lashay Alireza, Atyabi Fatemeh, Soleimani Masoud, Dinarvand Rassoul

机构信息

Translational Ophthalmology Research Centre, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Retina & Vitreous Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Ophthalmic Vis Res. 2022 Jan 21;17(1):58-68. doi: 10.18502/jovr.v17i1.10171. eCollection 2022 Jan-Mar.

DOI:10.18502/jovr.v17i1.10171
PMID:35194497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8850845/
Abstract

PURPOSE

The use of more potent medicine for local chemotherapy of retinoblastoma in order to minimize local and systemic adverse effects is essential. The main goal of this investigation was to assess the biodistribution of thiolated and methylated chitosan-carboxymethyl dextran nanoparticles (CMD-TCs-NPs and CMD-TMC-NPs) following intravitreal (IVT) injection into rat eyes with retinoblastoma.

METHODS

An ionic gelation method was used to fabricate Cy5-labelled CMD-TCs-NPs and CMD-TMC-NPs. The NPs were characterized. Cellular internalization of Cy5-labelled NPs was investigated using confocal microscopy and the absorption of labeled NPs was quantified by flow cytometry in human retinoblastoma (Y79) cells. In addition, the Cy5-labeled distribution of nanoparticles in the posterior segment of the eye was histologically imaged by confocal microscopy after IVT injection of NPs into the eyes of rats with retinoblastoma.

RESULTS

CMD-TCs-NPs and CMD-TMC-NPs showed a mean diameter of 34 3.78 nm and 42 4.23 nm and zeta potential of +11 2.27 mV and +29 4.31mV, respectively. The in vivo study of intraocular biodistribution of Cy5-labeled CMD-TCs-NPs and CMD-TMC-NPs revealed that there is more affinity of CMD-TCs-NPs to the retina and retinoblastoma tumor after IVT administration while methylated chitosan nanoparticles are immobilized in the vitreous and are not able to reach the retina even after 24 hr.

CONCLUSION

The ionic gelation technique was efficient in synthesizing a biocompatible polymeric nanosystem for drug delivery into the posterior segment of the eye. The current study demonstrated increased ocular bioavailability of CMD-TCs-NPs relative to CMD-TMC-NPs in retinoblastoma induced rat eyes.

摘要

目的

使用更强效的药物进行视网膜母细胞瘤的局部化疗以尽量减少局部和全身不良反应至关重要。本研究的主要目的是评估硫醇化和甲基化壳聚糖 - 羧甲基葡聚糖纳米颗粒(CMD - TCs - NPs和CMD - TMC - NPs)玻璃体内(IVT)注射入患有视网膜母细胞瘤的大鼠眼后其生物分布情况。

方法

采用离子凝胶法制备Cy5标记的CMD - TCs - NPs和CMD - TMC - NPs。对纳米颗粒进行表征。使用共聚焦显微镜研究Cy5标记纳米颗粒的细胞内化情况,并通过流式细胞术对人视网膜母细胞瘤(Y79)细胞中标记纳米颗粒的摄取进行定量。此外,将纳米颗粒玻璃体内注射入患有视网膜母细胞瘤的大鼠眼后,通过共聚焦显微镜对纳米颗粒在眼后段的Cy5标记分布进行组织学成像。

结果

CMD - TCs - NPs和CMD - TMC - NPs的平均直径分别为34 ± 3.78 nm和42 ± 4.23 nm,zeta电位分别为 +11 ± 2.27 mV和 +29 ± 4.31 mV。Cy5标记的CMD - TCs - NPs和CMD - TMC - NPs眼内生物分布的体内研究表明,玻璃体内给药后,CMD - TCs - NPs对视网膜和视网膜母细胞瘤肿瘤的亲和力更高,而甲基化壳聚糖纳米颗粒固定在玻璃体中,即使在24小时后也无法到达视网膜。

结论

离子凝胶技术有效地合成了一种用于将药物递送至眼后段的生物相容性聚合物纳米系统。当前研究表明,在视网膜母细胞瘤诱导的大鼠眼中,CMD - TCs - NPs相对于CMD - TMC - NPs具有更高的眼内生物利用度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/9b839ab6cb7a/jovr-17-58-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/7e4fa0074b37/jovr-17-58-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/43605a294f81/jovr-17-58-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/f5babaf7720d/jovr-17-58-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/58f2499ebe51/jovr-17-58-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/1168291e4af5/jovr-17-58-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/9b839ab6cb7a/jovr-17-58-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/7e4fa0074b37/jovr-17-58-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/43605a294f81/jovr-17-58-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/f5babaf7720d/jovr-17-58-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/58f2499ebe51/jovr-17-58-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/1168291e4af5/jovr-17-58-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/8850845/9b839ab6cb7a/jovr-17-58-g006.jpg

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