Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation
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 & Al...
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Dove Medical Press
2020
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oai:doaj.org-article:44aaf762688340f7a5c739aba36fc3902021-12-02T13:42:10ZCationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation1178-2013https://doaj.org/article/44aaf762688340f7a5c739aba36fc3902020-11-01T00:00:00Zhttps://www.dovepress.com/cationic-solid-lipid-nanoparticles-of-resveratrol-for-hepatocellular-c-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mahfoozur 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, YemenCorrespondence: Abdulsalam AlhalmiDepartment of Pharmaceutical Science, Collage of Pharmacy, Aden University, Aden, YemenCorrespondence Email aa.abdulla@pharm.adenuniv.comAim: 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 nitrosamineRahman MAlmalki WHAfzal OAlfawaz Altamimi ASKazmi IAl-Abbasi FAChoudhry HAlenezi SKBarkat MABeg SKumar VAlhalmi ADove Medical Pressarticleresveratrolcationic solid lipidsolid lipid nanoparticlesinflammatory biomarkershepatocellular carcinomadiethyl nitrosamineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 9283-9299 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
resveratrol cationic solid lipid solid lipid nanoparticles inflammatory biomarkers hepatocellular carcinoma diethyl nitrosamine Medicine (General) R5-920 |
| spellingShingle |
resveratrol cationic solid lipid solid lipid nanoparticles inflammatory biomarkers hepatocellular carcinoma diethyl nitrosamine Medicine (General) R5-920 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 Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation |
| description |
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, YemenCorrespondence: Abdulsalam AlhalmiDepartment of Pharmaceutical Science, Collage of Pharmacy, Aden University, Aden, YemenCorrespondence Email aa.abdulla@pharm.adenuniv.comAim: 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 |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Rahman M |
| title |
Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation |
| title_short |
Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation |
| title_full |
Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation |
| title_fullStr |
Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation |
| title_full_unstemmed |
Cationic Solid Lipid Nanoparticles of Resveratrol for Hepatocellular Carcinoma Treatment: Systematic Optimization, in vitro Characterization and Preclinical Investigation |
| title_sort |
cationic solid lipid nanoparticles of resveratrol for hepatocellular carcinoma treatment: systematic optimization, in vitro characterization and preclinical investigation |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/44aaf762688340f7a5c739aba36fc390 |
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