Role Of Anti-Apoptotic Activity Of Antioxidants In Conferring Protection Against Prostate Cancer

INTERNATIONAL JOURNAL OF PHARMACOLOGY(2016)

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摘要
The drug delivery potential of lipid and polymer based nano-carriers to achieving greater drug bioavailability has driven a renewed interest in their uptake mechanisms employed and movement within cells. Therefore, present study was designed to formulate resveratrol (Res) loaded Solid Lipid Nanoparticles (SLNs) as novel prototypes for prostate cancer treatment, to characterize and to assess the targeted and controlled delivery attributes of SLNs in human prostate cancer cells. The SLNs were prepared by a solvent diffusion evaporation method and characterized with respect to morphology, particle size and zeta potential, encapsulation and loading efficiency and in vitro release studies. Further, various process parameters were optimized for Res-loaded SLNs to obtain higher drug loading and entrapment efficiency with less than 200 nm uniform dispersity. The effects of free resveratrol (Res) and Res loaded SLNs (Res-SLNs) on internalization, cell uptake, viability, nucleosomal morphology, DNA fragmentation and Bcl-2 level was evaluated and compared with free Res on prostate cancer cells (PC-3). The immunofluorescence assay suggests that SLNs with a size lower than 175 nm showed rapid movement through cell membrane, distributes throughout the cytosol and moves successively among different cellular levels with minimal and acceptable cytotoxicity. The release profile of Res showed a bi-phasic pattern, showing its distribution in SLNs. The Res in solution was seen slightly cytotoxic and cytotoxicity was increased after encapsulating it in SLNs. Collectively, delivery of Res through SLNs contributes to effectiveness of Res on decreasing cell proliferation, with potential of inducing selective apoptosis of prostate cancer.
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关键词
Prostate cancer, solid lipid nanoparticles, resveratrol, apoptosis, oxidative stress
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