In vivo biodistribution, anti-inflammatory, and hepatoprotective effects of liver targeting dexamethasone acetate loaded nanostructured lipid carrier system.
We aimed to evaluate whether the enhancement of the liver accumulation and anti-inflammatory activity of dexamethasone acetate (DXMA) could be achieved by incorporating it into nanostructured lipid carrier (NLCs). DXMA-NLCs were prepared using a film dispersion-ultrasonication method and characterized in terms of particle size, PDI, zeta potential, differential scanning calorimetry, drug loading capacity, encapsulation efficiency, and in vitro release. The biodistribution and pharmacokinetics of DXMA-NLCs in mice were significantly different from those of the DXMA solution (DXMA-sol). The peak concentration of DXMA-NLCs was obtained half an hour after intravenous administration. More than 55.62% of the total administrated dose was present in the liver. An increase of 2.57 fold in the area under the curve was achieved when compared with that of DXMA-sol. DXMA-NLCs exhibited a significant anti-inflammatory and hepatoprotective effect on carrageenan-induced rats and carbon tetrachloride-induced mice compared with DXMA-sol. However, the effect was not in proportion to the dosage. The intermediate and low dosages presented better effects than DXMA-sol. All results indicate that NLCs, as a novel carrier for DXMA, has potential for the treatment of liver diseases, increasing the cure efficiency and decreasing the side effects on other tissues.
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China.
Min-ting
MT
Wang
Yun
Y
Jin
Yun-xia
YX
Yang
Chun-yan
CY
Zhao
Hong-yun
HY
Yang
Xue-fan
XF
Xu
Xuan
X
Qin
Zhao-dan
ZD
Wang
Zhi-rong
ZR
Zhang
Yan-lin
YL
Jian
Yuan
Y
Huang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002351:Carrageenan / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008107:Liver Diseases / Q000188:drug therapy; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008081:Liposomes; D003907:Dexamethasone; D002351:Carrageenan; D002251:Carbon Tetrachloride; C018038:dexamethasone acetate