Toxicogenomics of nanoparticulate delivery of etoposide: potential impact on nanotechnology in retinoblastoma therapy

Cancer Nanotechnology

Original Paper

Anju Harilal¹  Subramanian Krishnakumar¹  Moutushy Mitra²  Rama Shenkar Verma³  Fahima Dilnawaz⁴  Ranjita Misra⁴  Sanjeeb K. Sahoo⁴ 

[1] Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, No 18 College Road, Nungambakkam, 600006, Chennai, India;Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, No 18 College Road, Nungambakkam, 600006, Chennai, India;CeNTAB, Sastra University, Tanjore, India;Indian Institute of Technology, Madras, India;Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, Orissa, India;

关键词: Retinoblastoma;    Ocular drug delivery;    PLGA nanoparticles;    Apoptosis;    Gene expression;   

DOI  :  10.1007/s12645-010-0010-4

 received in 2010-10-19, accepted in 2010-11-28,  发布年份 2010

来源: Springer

【 摘 要 】

To develop a suitable formulation with high entrapment efficiency, etoposide-loaded poly(lactide-co-glycolide) nanoparticles (NPs) were formulated by single emulsion-solvent evaporation method by changing different formulation parameters such as drug loading, choice of organic solvent and percentage of emulsifier polyvinyl alcohol. The NPs showed higher entrapment efficiency, ~86% (with 15% (w/w) drug loading). The physicochemical parameters revealed smooth topology with size range (240–320 nm), a negative zeta potential (~19 mV) and in vitro sustained-release activity (~60% drug release in 40 days). Greater anti-proliferative activity ~100 times was observed with NPs (IC50 = 0.002 μg/ml) than that of native etoposide (IC50 = 0.2 μg/ml) in retinoblastoma cell line (Y-79). These NPs demonstrated greater (G1/S) blocking and decreased mitochondrial membrane potential as measured by flow cytometry. There was upregulation of apoptotic gene activity in NPs than native etoposide, as revealed through microarray analysis. However, this is the first ever report demonstrating the intricate modulation of genetic network affected by NPs. Collectively, these results suggest that etoposide-loaded NPs could be potentially useful as a novel drug delivery system for retinoblastoma in the future.FigureNanoparticle-mediated etoposide delivery promotes apoptosis through upregulating several apoptotic inducer genes

【 授权许可】

Unknown   
© Springer-Verlag 2010