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 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.
Laboratory of Nanomedicine, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751 023, Orissa, India.
Suphiya
S
Parveen
Moutushy
M
Mitra
S
S
Krishnakumar
Sanjeeb K
SK
Sahoo
D000464:Alginates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D016190:Carboplatin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012175:Retinoblastoma / Q000473:pathology*; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D048271:Chitosan; D016190:Carboplatin