Biodistribution studies of CY5-labeled thiolated and methylated chitosan-dextran nanoparticles intended for designing ideal drug delivery system for retinoblastoma treatment
Elham Delrish1 , Fariba Ghassemi 2 , Mahmoud Jabbarvand 1 *, Alireza Lashay 1 , Fatemeh Atyabi 3 , Masoud Soleimani 4 , Rassoul Dinarvand 5
- Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
- 1-Translational Ophthalmology Research Centre (TORC), Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran. 2- Retina & Vitreous Service, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
- 3-Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 4-Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- 5-Department of Hematology, School of Medical Sciences, TarbiatModares University, Tehran, Iran.
- 3- Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 4-Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Abstract: Retinoblastoma (Rb) is the most common intraocular malignancy in childhood. Since chemotherapy is the most common treatment option for retinoblastoma, the production of effective carriers for drug delivery to the posterior segment of the eye with a focus on minimizing local and systemic side effects has always been an area of debate. The main objective of this investigation was to study the biodistribution of the CY5-labeled thiolated and methylated chitosan-carboxymethyl dextran nanoparticles (CMD-TCs-NPs and CMD-TMC-NPs) after intravitreal injection into the rat eyes with retinoblastoma.
Methods: 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 intravitreal injection of NPs into the ratretinoblastoma containing eyes.
Results: CMD-TCs-NPs and CMD-TMC-NPs showed a mean diameter of 34±3.78 nm and 42±4.23nm 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 more affinity of CMD-TCs-NPs to the retina and retinoblastoma tumor after intravitreal administration while methylated chitosan nanoparticles are immobilized in the vitreous and are not able to reach the retina even after 24 hours.
Conclusion: The ionic gelation technique was efficient in synthesizing a biocompatible polymeric nano system for drug delivey to the posterior segment of the eye. The current investigation demonstrated enhanced ocular bioavilibility of CMD-TCs-NPs relative to CMD-TMC-NPs in retinoblastoma induced rat eyes.
