TY - JOUR
T1 - Silymarin loaded liposomes for hepatic targeting
T2 - In vitro evaluation and HepG2 drug uptake
AU - Elmowafy, Mohammed
AU - Viitala, Tapani
AU - Ibrahim, Hany M.
AU - Abu-Elyazid, Sherif K.
AU - Samy, Ahmed
AU - Kassem, Alaa
AU - Yliperttula, Marjo
N1 - Funding Information:
This research was funded by Center for International Mobility (CIMO, Egypt , Grant No. KM-12-8148 ) and Academy of Finland (Grant Nos. 137053 and 140980 ). We also want to address our special thanks to Tatiana Elizarova for her kind help in the experimental work of the cell uptake studies.
PY - 2013
Y1 - 2013
N2 - Silymarin has hepatoprotective properties and is used in treatment of various liver diseases, but its bioavailability from oral products is very poor. In order to overcome its poor oral bioavailability we have prepared silymarin loaded hepatic targeting liposomes suitable for parenteral administration. The liposomal formulations were composed of hydrogenated soy phosphatidylcholine and cholesterol with or without distearoylphosphoethanolamine-(polyethyleneglycol)- 2000 and various amounts of β-sitosterol b-D-glucoside (Sito-G) as the hepatic targeting moiety. Increasing the amount of Sito-G in the liposomes gradually decreased drug encapsulation efficiencies from ~70% to ~60%; still showing promising drug encapsulation efficiencies. Addition of Sito-G to non-PEGylated liposomes clearly affected their drug release profiles and plasma protein interactions, whereas no effect on these was seen for the PEGylated liposomes. Non-PEGylated liposomes with 0.17 M ratio of Sito-G exhibited the highest cellular drug uptake of 37.5% for all of the studied liposome formulations. The highest cellular drug uptake in the case of PEGylated liposomes was 18%, which was achieved with 0.17 and 0.33 M ratio of added Sito-G. The liposome formulations with the highest drug delivery efficacy in this study showed hemolytic activities around 12.7% and were stable for at least 2 months upon storage in 20 mM HEPES buffer (pH 7.4) containing 1.5% Polysorbate 80 at 4 °C and room temperature. These results suggest that the Sito-G containing liposomes prepared in this work have hepatic targeting capability and that they are promising candidates for delivering silymarin to the liver.
AB - Silymarin has hepatoprotective properties and is used in treatment of various liver diseases, but its bioavailability from oral products is very poor. In order to overcome its poor oral bioavailability we have prepared silymarin loaded hepatic targeting liposomes suitable for parenteral administration. The liposomal formulations were composed of hydrogenated soy phosphatidylcholine and cholesterol with or without distearoylphosphoethanolamine-(polyethyleneglycol)- 2000 and various amounts of β-sitosterol b-D-glucoside (Sito-G) as the hepatic targeting moiety. Increasing the amount of Sito-G in the liposomes gradually decreased drug encapsulation efficiencies from ~70% to ~60%; still showing promising drug encapsulation efficiencies. Addition of Sito-G to non-PEGylated liposomes clearly affected their drug release profiles and plasma protein interactions, whereas no effect on these was seen for the PEGylated liposomes. Non-PEGylated liposomes with 0.17 M ratio of Sito-G exhibited the highest cellular drug uptake of 37.5% for all of the studied liposome formulations. The highest cellular drug uptake in the case of PEGylated liposomes was 18%, which was achieved with 0.17 and 0.33 M ratio of added Sito-G. The liposome formulations with the highest drug delivery efficacy in this study showed hemolytic activities around 12.7% and were stable for at least 2 months upon storage in 20 mM HEPES buffer (pH 7.4) containing 1.5% Polysorbate 80 at 4 °C and room temperature. These results suggest that the Sito-G containing liposomes prepared in this work have hepatic targeting capability and that they are promising candidates for delivering silymarin to the liver.
KW - Hepatic targeting
KW - HepG2
KW - Silymarin
KW - Targeting liposomes
KW - β-Sitosterol β-D-glucoside
UR - http://www.scopus.com/inward/record.url?scp=84881181698&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2013.06.012
DO - 10.1016/j.ejps.2013.06.012
M3 - Article
C2 - 23851081
AN - SCOPUS:84881181698
SN - 0928-0987
VL - 50
SP - 161
EP - 171
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 2
ER -