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Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells
Authors:Anmar M. Nassir  Naiyer Shahzad  Ibrahim A.A. Ibrahim  Iqbal Ahmad  Shadab Md  Mohammad R. Ain
Affiliation:1. Department of Surgery, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia;2. Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia;3. Nanomedicine Research Lab., Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India;4. Advance Nanomeds, NSEZ, Noida, Uttar Pradesh, India;5. Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Jalil Perkasa, Kuala Lumpur, Malaysia;6. Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia
Abstract:Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6?±?1.49 and 41.1?±?2.19?μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200?μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.
Keywords:Resveratrol  PLGA nanoparticles  Prostate cancer  LNCaP cells  Apoptosis  Drug delivery
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