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.
Wang
Min-ting
MT
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.
Jin
Yun
Y
Yang
Yun-xia
YX
Zhao
Chun-yan
CY
Yang
Hong-yun
HY
Xu
Xue-fan
XF
Qin
Xuan
X
Wang
Zhao-dan
ZD
Zhang
Zhi-rong
ZR
Jian
Yan-lin
YL
Huang
Yuan
Y
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