Dataset Information

Drug Displacement Strategy for Treatment of Acute Liver Injury with Cyclodextrin-Liposome Nanoassembly.

ABSTRACT: Biofunctional supramolecular assemblies that combine macrocyclic receptors and amphiphiles are potent drug delivery systems, but optimization and implementation challenges remain. We herein describe a cooperative drug displacement strategy exemplified by the use of cyclodextrin-liposome supramolecular nanoassemblies as a therapy for acute liver injury. The hepatoprotective drug silibinin was solubilized in phosphotyramine-modified ?-cyclodextrin, and subsequent encapsulation of the silibinin-cyclodextrin complex in phosphatidylcholine liposomes gave uniformly sized and stable nanoassemblies that accumulated preferentially in the liver of mice. Enzymatic cleavage of the phosphate ester of the ?-cyclodextrin resulted in rapid release of the encapsulated silibinin. Significantly, silibinin could be readily displaced by cytotoxic bile acids, thus leading to the removal of excess bile acids from the bodies of mice and the recovery of liver function. Our results demonstrate that cyclodextrin-based nanoassemblies with a dual role of solubilizing a drug and removing toxins constitute a promising therapy for hepatic injury.

SUBMITTER: Zhang YM

PROVIDER: S-EPMC6515158 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Drug Displacement Strategy for Treatment of Acute Liver Injury with Cyclodextrin-Liposome Nanoassembly.

Zhang Ying-Ming YM Xu Xun X Yu Qilin Q Yu Hua-Jiang HJ Liu Yu Y

iScience 20190426

Biofunctional supramolecular assemblies that combine macrocyclic receptors and amphiphiles are potent drug delivery systems, but optimization and implementation challenges remain. We herein describe a cooperative drug displacement strategy exemplified by the use of cyclodextrin-liposome supramolecular nanoassemblies as a therapy for acute liver injury. The hepatoprotective drug silibinin was solubilized in phosphotyramine-modified β-cyclodextrin, and subsequent encapsulation of the silibinin-cyc ...[more]

PMID: 31079026

Similar Datasets

Project description:Background & aimsChronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity.Methods298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition.ResultsOut of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis.ConclusionsOne year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery.Lay summaryDrug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.

Dataset Information

Drug Displacement Strategy for Treatment of Acute Liver Injury with Cyclodextrin-Liposome Nanoassembly.

Publications

Drug Displacement Strategy for Treatment of Acute Liver Injury with Cyclodextrin-Liposome Nanoassembly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets