Impact of Reverse Micelle Loaded Lipid Nanocapsules on the Delivery of Gallic Acid into Activated Hepatic Stellate Cells
- PDF / 2,749,176 Bytes
- 17 Pages / 595.276 x 790.866 pts Page_size
- 52 Downloads / 175 Views
RESEARCH PAPER
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 Shaimaa Ali Ali Radwan 1 Carol Yousry 1
2
1
1
& Walaa H. El-Maadawy & Aliaa Nabil ElMeshad & Raguia Aly Shoukri &
Received: 26 May 2020 / Accepted: 23 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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; GARMLNC displayed higher anti-proliferative activities,
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11095-020-02891-z) contains supplementary material, which is available to authorized users. * Shaimaa Ali Ali Radwan [email protected]
1
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al Aini street, PO Box 11562, Cairo, Egypt
2
Department of Pharmacology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt
effective internalization into aHSCs, marked downregulation 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.
KEYWORDS Gallic acid . hepatic fibrosis . hepatic stellate cells . reverse micelle loaded lipid nanocapsules . passive targeting
ABBREVIATIONS ANOVA aHSCs cDNA COL1A1 DAPI DMEM ECM EE% FBS GA HBSS HPLC KH2PO4 LNC Na2HPO4 NP PBS PDI PIT PS Q2h
Analysis of variance activated Hepatic stellate cells Complementary DNA Collagen type I 4′,6-diamidino-2-phenylindole Dulbecco’s Modified Eagle’s Medium Extracellular matrix Entrapment efficiency percentage Fetal bovine serum Gallic acid Hanks Balanced Salt Solution High performan
Data Loading...
