Impact of Reverse Micelle Loaded Lipid Nanocapsules on the Delivery of Gallic Acid into Activated Hepatic Stellate Cells: A Promising Therapeutic Approach for Hepatic Fibrosis

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2020 Sep 3

PMID 32875435

Citations 8

Authors

Shaimaa Ali Ali Radwan

Walaa H El-Maadawy

Aliaa Nabil ElMeshad

Raguia Aly Shoukri

Carol Yousry

Affiliations

Soon will be listed here.

Abstract

Purpose: Gallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression.

Methods: GA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored.

Results: Nano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats' livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities, effective internalization into aHSCs, marked down-regulation in pro-fibrogenic biomarkers' expressions and elevated HSCs' apoptosis.

Conclusions: These findings emphasize the promising application of RMLNC as a delivery system in hepatic fibrosis treatment, where successful delivery of GA into aHSCs was ensured via increased cellular uptake and antifibrotic activities.

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References

Poynard T, Lebray P, Ingiliz P, Varaut A, Varsat B, Ngo Y . Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest). BMC Gastroenterol. 2010; 10:40. PMC: 2864202. DOI: 10.1186/1471-230X-10-40. View

Constantinides P . Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995; 12(11):1561-72. DOI: 10.1023/a:1016268311867. View

Schon H, Bartneck M, Borkham-Kamphorst E, Nattermann J, Lammers T, Tacke F . Pharmacological Intervention in Hepatic Stellate Cell Activation and Hepatic Fibrosis. Front Pharmacol. 2016; 7:33. PMC: 4764688. DOI: 10.3389/fphar.2016.00033. View

Kisseleva T . The origin of fibrogenic myofibroblasts in fibrotic liver. Hepatology. 2016; 65(3):1039-1043. PMC: 5476301. DOI: 10.1002/hep.28948. View

El-Mezayen N, El-Hadidy W, El-Refaie W, Shalaby T, Khattab M, El-Khatib A . Hepatic stellate cell-targeted imatinib nanomedicine versus conventional imatinib: A novel strategy with potent efficacy in experimental liver fibrosis. J Control Release. 2017; 266:226-237. DOI: 10.1016/j.jconrel.2017.09.035. View

Yu K, Li N, Cheng Q, Zheng J, Zhu M, Bao S . miR-96-5p prevents hepatic stellate cell activation by inhibiting autophagy via ATG7. J Mol Med (Berl). 2017; 96(1):65-74. DOI: 10.1007/s00109-017-1593-6. View

Iwakiri Y, Shah V, Rockey D . Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions. J Hepatol. 2014; 61(4):912-24. PMC: 4346093. DOI: 10.1016/j.jhep.2014.05.047. View

DeLeve L . Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology. 2014; 61(5):1740-6. PMC: 4333127. DOI: 10.1002/hep.27376. View

Chen Z, Jain A, Liu H, Zhao Z, Cheng K . Targeted Drug Delivery to Hepatic Stellate Cells for the Treatment of Liver Fibrosis. J Pharmacol Exp Ther. 2019; 370(3):695-702. PMC: 6806344. DOI: 10.1124/jpet.118.256156. View

10.

Abdou E, Masoud M . Gallic acid-PAMAM and gallic acid-phospholipid conjugates, physicochemical characterization and in vivo evaluation. Pharm Dev Technol. 2017; 23(1):55-66. DOI: 10.1080/10837450.2017.1344994. View

11.

Kaur M, Velmurugan B, Rajamanickam S, Agarwal R, Agarwal C . Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharm Res. 2009; 26(9):2133-40. PMC: 2741017. DOI: 10.1007/s11095-009-9926-y. View

12.

Kim Y . Antimelanogenic and antioxidant properties of gallic acid. Biol Pharm Bull. 2007; 30(6):1052-5. DOI: 10.1248/bpb.30.1052. View

13.

Liu K, Hu S, Chan B, Wat E, Lau C, Hon K . Anti-inflammatory and anti-allergic activities of Pentaherb formula, Moutan Cortex (Danpi) and gallic acid. Molecules. 2013; 18(3):2483-500. PMC: 6270292. DOI: 10.3390/molecules18032483. View

14.

Faried A, Kurnia D, Faried L, Usman N, Miyazaki T, Kato H . Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines. Int J Oncol. 2007; 30(3):605-13. DOI: 10.3892/ijo.30.3.605. View

15.

El-Lakkany N, El-Maadawy W, Seif El-Din S, Saleh S, Safar M, Ezzat S . Antifibrotic effects of gallic acid on hepatic stellate cells: mechanistic study. J Tradit Complement Med. 2019; 9(1):45-53. PMC: 6335492. DOI: 10.1016/j.jtcme.2018.01.010. View

16.

Sourani Ms Z, Pourgheysari PhD B, Beshkar Ms P, Shirzad PhD H, Shirzad Ms M . Gallic Acid Inhibits Proliferation and Induces Apoptosis in Lymphoblastic Leukemia Cell Line (C121). Iran J Med Sci. 2016; 41(6):525-530. PMC: 5106568. View

17.

Sun G, Zhang S, Xie Y, Zhang Z, Zhao W . Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells. Oncol Lett. 2016; 11(1):150-158. PMC: 4727056. DOI: 10.3892/ol.2015.3845. View

18.

Chen G, Roy I, Yang C, Prasad P . Nanochemistry and Nanomedicine for Nanoparticle-based Diagnostics and Therapy. Chem Rev. 2016; 116(5):2826-85. DOI: 10.1021/acs.chemrev.5b00148. View

19.

Fan Q, Zhang C, Qiao J, Cui P, Xing L, Oh Y . Extracellular matrix-penetrating nanodrill micelles for liver fibrosis therapy. Biomaterials. 2019; 230:119616. DOI: 10.1016/j.biomaterials.2019.119616. View

20.

Levada K, Omelyanchik A, Rodionova V, Weiskirchen R, Bartneck M . Magnetic-Assisted Treatment of Liver Fibrosis. Cells. 2019; 8(10). PMC: 6830324. DOI: 10.3390/cells8101279. View