April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Polymer Genomics: Beneficial Influence in the Delivery of Etoposide to Retinoblastoma Cells
Author Affiliations & Notes
  • S. Krishnakumar
    L & T Ocular Pathology,
    Vision Research Foundation,, Chennai, India
  • M. Moutushy
    L & T Ocular Pathology,
    Vision Research Foundation,, Chennai, India
  • H. Anju
    L & T Ocular Pathology,
    Vision Research Foundation,, Chennai, India
  • S. K. Sahoo
    Nanomedicine Laboratory, Institute of Life Sciences, Bhubaneswar, Orissa, India
  • M. Kandalam
    L & T Ocular Pathology,
    Vision Research Foundation,, Chennai, India
  • L. Gopal
    Ocular Oncology,
    Vision Research Foundation,, Chennai, India
  • V. Khetan
    Ocular Oncology,
    Vision Research Foundation,, Chennai, India
  • M. Vasudevan
    Genomics & Bio-IT,, Genotypic Technology Pvt. Ltd., Bangalore, India
  • J. Biswas
    L & T Ocular Pathology,
    Vision Research Foundation,, Chennai, India
  • Footnotes
    Commercial Relationships  S. Krishnakumar, None; M. Moutushy, None; H. Anju, None; S.K. Sahoo, None; M. Kandalam, None; L. Gopal, None; V. Khetan, None; M. Vasudevan, None; J. Biswas, None.
  • Footnotes
    Support  ICMR Grant 58/12/2005-BMS
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2065. doi:
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      S. Krishnakumar, M. Moutushy, H. Anju, S. K. Sahoo, M. Kandalam, L. Gopal, V. Khetan, M. Vasudevan, J. Biswas; Polymer Genomics: Beneficial Influence in the Delivery of Etoposide to Retinoblastoma Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2065.

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Abstract

Purpose: : We studied the influence of polymeric nanoparticles entrapped with etoposide versus native drug on the gene expression profile of the retinoblastoma cells using microarray

Methods: : The chemotherapy drug loaded nanoparticles were formulated by single oil-in-water emulsion solvent evaporation method. Different formulation parameters such as, amount of drug loading (w/w), solvent selection, amount of emulsifier were employed for the greater entrapment efficiency of the drug in nanoparticular formulations. The nanoparticles were further characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). We studied the cellular uptake, affect on apoptosis and gene expression profile using agilent microarray

Results: : The batch analysis showed that the formulation of nanoparticles in chloroform with 5 % (w/v) poly vinyl alcohol (PVA), 15 % (w/w) drug loading showed greater entrapment efficiency up to ~ 86 %. The drug loaded nanoparticles were in the size range of 260 -320 nm, with a zeta potential range of -14 to - 25 mV. The in vitro release studies showed a sustained release activity of the drug from the formulated nanoparticles in two weeks. The drug loaded nanoparticles demonstrated greater and sustained antiproliferative activity of the drug as compared to the drug in solution in the retinoblastoma cell line (Y-79).

Conclusions: : The higher cytotoxic and apoptotic effect of etoposide loaded nanoparticles may be due to their greater cellular uptake (6 folds as compared to native drug). The cDNA array profiles demonstrated that drug nanoparticle treatment primarily up-regulated the expression of three groups of potential genes related to cell cycle and cell differentiation, apoptosis (BAD, NFK1A), transporter protein (ABCA5) and few anti-angiogenesis (TIMP2) related genes. These changes were coupled with down regulation of few oncogenes (RAB36) and genes responsible for proliferation. Amongst them 8 number of genes are upregulated more than one fold in apoptosis, while the gene for both apoptosis and angiogenesis transcription factor (ELF3) increases 3 fold. Thus polymeric nanoparticle entrapped drug appears more effective than the native drug on the retinoblastoma cells. Further studies are needed to understand the role of polymer genomics in the drug delivery to retinoblastoma.

Keywords: gene microarray • retinoblastoma • tumors 
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