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Targeted Delivery of Anticancer Drug Loaded Charged PLGA Polymeric Nanoparticles Using Electrostatic Field
Authors:Seyyed Hossein Miraghaie  Ashkan Zandi  Zahra Davari  Mohamad Sadegh Mousavi-kiasary  Zohre Saghafi  Ali Gilani  Yasin Kordehlachin  Fatemeh Shojaeian  Amir Mamdouh  Zahra Heydari  Farid Abedin Dorkoosh  Babak Kaffashi  Mohammad Abdolahad
Affiliation:1. Department of Polymer Engineering, Kish International Campus, University of Tehran, Kish Island, 79416-55664 Iran

Nano Electronic Center of Excellence, Nano-bioelectronic Devices Lab., Cancer Electronics Research Group, School of Electrical and Computer Eng., College of Engineering, University of Tehran, Tehran, 14395–515 Iran

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14176-14411 Iran;2. Nano Electronic Center of Excellence, Nano-bioelectronic Devices Lab., Cancer Electronics Research Group, School of Electrical and Computer Eng., College of Engineering, University of Tehran, Tehran, 14395–515 Iran

Nano Electronic Center of Excellence, Nano-electronics and Thin Film Lab., School of Electrical and Computer Eng., College of Engineering, University of Tehran, Tehran, 14395–515 Iran;3. Nano Electronic Center of Excellence, Nano-bioelectronic Devices Lab., Cancer Electronics Research Group, School of Electrical and Computer Eng., College of Engineering, University of Tehran, Tehran, 14395–515 Iran

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14176-14411 Iran;4. Nano Electronic Center of Excellence, Nano-bioelectronic Devices Lab., Cancer Electronics Research Group, School of Electrical and Computer Eng., College of Engineering, University of Tehran, Tehran, 14395–515 Iran;5. Nano Electronic Center of Excellence, Nano-bioelectronic Devices Lab., Cancer Electronics Research Group, School of Electrical and Computer Eng., College of Engineering, University of Tehran, Tehran, 14395–515 Iran

School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 19615-1179 Iran;6. Preclinical lab, Core facility, Tehran University of Medical Sciences, Tehran, 14174-66191 Iran;7. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14176-14411 Iran;8. Department of Polymer Engineering, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, 11155-4563 Iran

Abstract:Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg−1] versus DLNs-based chemotherapy [0.75 mg kg−1]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.
Keywords:animal study  cancer  charged polymeric nano-particles  electrostatic field  optimized chemotherapy  targeted drug delivery
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