Enhanced antiproliferative activity of carboplatin-loaded chitosan-alginate nanoparticles in a retinoblastoma cell line

In the present study the potential of carboplatin-loaded chitosan-alginate nanoparticles (CANPs) for the treatment of retinoblastoma was investigated. The carboplatin-loaded CANPs were approximately 300 nm in size, exhibited a high zeta potential of approximately 36 mV and drug encapsulation of appr...

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Bibliographic Details
Published in:Acta biomaterialia 2010-08, Vol.6 (8), p.3120-3131
Main Authors: Parveen, Suphiya, Mitra, Moutushy, Krishnakumar, S, Sahoo, Sanjeeb K
Format: Article
Language:English
Subjects:
Alginates - chemistry
Calorimetry, Differential Scanning
Carboplatin - pharmacology
Cell Death - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Chitosan - chemistry
Dose-Response Relationship, Drug
Glucuronic Acid - chemistry
Hexuronic Acids - chemistry
Humans
Intracellular Space - drug effects
Intracellular Space - metabolism
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Particle Size
Retinoblastoma - pathology
Spectroscopy, Fourier Transform Infrared
Time Factors
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Summary:In the present study the potential of carboplatin-loaded chitosan-alginate nanoparticles (CANPs) for the treatment of retinoblastoma was investigated. The carboplatin-loaded CANPs were approximately 300 nm in size, exhibited a high zeta potential of approximately 36 mV and drug encapsulation of approximately 20 wt.%. The CANPs were further characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and transmission electron microscopy. In vitro release studies revealed fast release of approximately 25% of the drug during the first 24h, followed by sustained release. CANPs demonstrated greater and sustained antiproliferative activity of the drug in a dose- and time-dependent manner (carboplatin IC(50)=0.56 microg ml(-1), carboplatin-loaded CANPs IC(50)=0.004 microg ml(-1)), as well as an enhanced apoptotic effect as compared with the drug in solution in a retinoblastoma cell line (Y79). The higher cytotoxic effect of CANPs may be due to their greater cellular uptake as compared with native carboplatin. It was also demonstrated that clathrin-mediated endocytosis plays a key role in the internalization of CANPs in the Y79 cell line. In conclusion, biodegradable chitosan nanoparticles could be used as an effective ocular drug delivery system for sustained intracellular delivery of carboplatin for the treatment of retinoblastoma.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2010.02.010