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Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation

Authors Rahman M, Almalki WH, Afzal O, Alfawaz Altamimi AS, Kazmi I, Al-Abbasi FA, Choudhry H, Alenezi SK, Barkat MA, Beg S, Kumar V, Alhalmi A

Received 24 August 2020

Accepted for publication 29 October 2020

Published 23 November 2020 Volume 2020:15 Pages 9283—9299

DOI https://doi.org/10.2147/IJN.S277545

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster


Mahfoozur Rahman,1 Waleed H Almalki,2 Obaid Afzal,3 Abdulmalik Saleh Alfawaz Altamimi,3 Imran Kazmi,4 Fahad A Al-Abbasi,4 Hani Choudhry,5 Sattam K Alenezi,6 Md Abul Barkat,7 Sarwar Beg,8 Vikas Kumar,1 Abdulsalam Alhalmi9

1Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India; 2Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 3Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj 11942, Saudi Arabia; 4Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Biochemistry, Cancer Metabolism & Epigenetic Unit, Faculty of Science, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Pharmacology & Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim, Saudi Arabia; 7Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Al Jamiah, Hafr Al Batin, Saudi Arabia; 8Department of Pharmaceutics, School of Pharmaceutical Education and Research, Nanomedicine Research Lab, Jamia Hamdard, New Delhi, India; 9Department of Pharmaceutical Science, Collage of Pharmacy, Aden University, Aden, Yemen

Correspondence: Abdulsalam Alhalmi
Department of Pharmaceutical Science, Collage of Pharmacy, Aden University, Aden, Yemen
Correspondence Email aa.abdulla@pharm.adenuniv.com

Aim: The present study focuses on the development and evaluation of the resveratrol (RV)-loaded cationic solid lipid nanoparticles (RV-c-SLNs) for the management of hepatocellular carcinoma (HCC).
Materials and Methods: Optimization of formulation was performed using factorial design, and further in vitro drug release, cytotoxicity, biodistribution, in vivo preclinical, and biochemical evaluation were carried out.
Results: The optimized formulation exhibited uniform size, homogeneous disparity, positive zeta potential, and stability over 12-week storage at 25°C/60% RH. The in vitro drug release and cytotoxicity study showed 60% drug release within the first 6 hours and comparatively higher cytotoxicity on HepG2 cell line by resveratrol-solid lipid nanoparticle (RV-SLN) as compared to the RV solution. In addition, an anticancer action and biodistribution study on a rat model of HCC showed significant reduction of tumor volume and higher accumulation in the tumor tissue from RV-c-SLN (P< 0.01) over RV solution and RV-SLN. Furthermore, RV-c-SLN showed significant down-regulation in the levels of pro-inflammatory cytokines and balancing of antioxidant enzymes. Histopathological investigation showed reduced occurrence of hepatic nodules, necrosis formation, infiltration of inflammatory cells, blood vessels inflammation, and cell swelling.
Conclusion: Overall, the obtained results construed that RV-c-SLN with improved antitumor activity as clearly evident from in vitro, in vivo, and biochemical investigations.

Keywords: resveratrol, cationic solid lipid, solid lipid nanoparticles, inflammatory biomarkers, hepatocellular carcinoma, diethyl nitrosamine

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