Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin

Yue Yuan,1,2 Jian Wen,3 Jie Tang,2 Qiming Kan,1 Rose Ackermann,2 Karl Olsen,2 Anna Schwendeman2 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmaceutical Sciences, Biointerfaces Institute, Coll...

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Autores principales:	Yuan Y, Wen J, Tang J, Kan Q, Ackermann R, Olsen K, Schwendeman A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	10-hydroxycamptothecin (HCPT) high density lipoprotein (HDL) apolipoprotein A-I mimic peptide phospholipids SR-BI receptor colon carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f06102dde2dd43db9b6f5c205edf356b
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spelling	oai:doaj.org-article:f06102dde2dd43db9b6f5c205edf356b2021-12-02T03:05:26ZSynthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin1178-2013https://doaj.org/article/f06102dde2dd43db9b6f5c205edf356b2016-11-01T00:00:00Zhttps://www.dovepress.com/synthetic-high-density-lipoproteins-for-delivery-of-10-hydroxycamptoth-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yue Yuan,1,2 Jian Wen,3 Jie Tang,2 Qiming Kan,1 Rose Ackermann,2 Karl Olsen,2 Anna Schwendeman2 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmaceutical Sciences, Biointerfaces Institute, College of Pharmacy, University of Michigan, 3Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI, USA Abstract: The purpose of this study was to develop a novel synthetic high-density lipoprotein (sHDL) nanoparticle delivery system for 10-hydroxycamptothecin (HCPT) for treatment of colon carcinoma. HDL is recognized by scavenger receptor B-I (SR-BI) over-expressed in colon carcinomas 5- to 35-fold relative to the human fibroblasts. The sHDL nanoparticles were composed of apolipoprotein A-I mimic peptide (5A) and contained 0.5%–1.5% (w/w) of HCPT. An optimized HCPT-sHDL formulation exhibited 0.7% HCPT loading with 70% efficiency with an average size of 10–12 nm. Partitioning of HCPT in the sHDL lipid membrane enhanced drug stability in its active lactone form, increased solubilization, and enabled slow release. Cytotoxicity studies in HT29 colon carcinoma cells revealed that the IC50 of HCPT-sHDL was approximately 3-fold lower than that of free HCPT. Pharmacokinetics in rats following intravenous administration showed that the area under the serum concentration-time curve (AUC0–t) and Cmax of HCPT-HDL were 2.7- and 6.5-fold higher relative to the values for the free HCPT, respectively. These results suggest that sHDL-based formulations of hydrophobic drugs are useful for future evaluation in treatment of SR-BI-positive tumors. Keywords: apolipoprotein A-I mimic peptide, phospholipids, SR-BI receptor, colon carcinoma, camptothecin, nanoparticle, nanodiscYuan YWen JTang JKan QAckermann ROlsen KSchwendeman ADove Medical Pressarticle10-hydroxycamptothecin (HCPT)high density lipoprotein (HDL)apolipoprotein A-I mimic peptidephospholipidsSR-BI receptorcolon carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6229-6238 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	10-hydroxycamptothecin (HCPT) high density lipoprotein (HDL) apolipoprotein A-I mimic peptide phospholipids SR-BI receptor colon carcinoma Medicine (General) R5-920
spellingShingle	10-hydroxycamptothecin (HCPT) high density lipoprotein (HDL) apolipoprotein A-I mimic peptide phospholipids SR-BI receptor colon carcinoma Medicine (General) R5-920 Yuan Y Wen J Tang J Kan Q Ackermann R Olsen K Schwendeman A Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
description	Yue Yuan,1,2 Jian Wen,3 Jie Tang,2 Qiming Kan,1 Rose Ackermann,2 Karl Olsen,2 Anna Schwendeman2 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmaceutical Sciences, Biointerfaces Institute, College of Pharmacy, University of Michigan, 3Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI, USA Abstract: The purpose of this study was to develop a novel synthetic high-density lipoprotein (sHDL) nanoparticle delivery system for 10-hydroxycamptothecin (HCPT) for treatment of colon carcinoma. HDL is recognized by scavenger receptor B-I (SR-BI) over-expressed in colon carcinomas 5- to 35-fold relative to the human fibroblasts. The sHDL nanoparticles were composed of apolipoprotein A-I mimic peptide (5A) and contained 0.5%–1.5% (w/w) of HCPT. An optimized HCPT-sHDL formulation exhibited 0.7% HCPT loading with 70% efficiency with an average size of 10–12 nm. Partitioning of HCPT in the sHDL lipid membrane enhanced drug stability in its active lactone form, increased solubilization, and enabled slow release. Cytotoxicity studies in HT29 colon carcinoma cells revealed that the IC50 of HCPT-sHDL was approximately 3-fold lower than that of free HCPT. Pharmacokinetics in rats following intravenous administration showed that the area under the serum concentration-time curve (AUC0–t) and Cmax of HCPT-HDL were 2.7- and 6.5-fold higher relative to the values for the free HCPT, respectively. These results suggest that sHDL-based formulations of hydrophobic drugs are useful for future evaluation in treatment of SR-BI-positive tumors. Keywords: apolipoprotein A-I mimic peptide, phospholipids, SR-BI receptor, colon carcinoma, camptothecin, nanoparticle, nanodisc
format	article
author	Yuan Y Wen J Tang J Kan Q Ackermann R Olsen K Schwendeman A
author_facet	Yuan Y Wen J Tang J Kan Q Ackermann R Olsen K Schwendeman A
author_sort	Yuan Y
title	Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
title_short	Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
title_full	Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
title_fullStr	Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
title_full_unstemmed	Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
title_sort	synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/f06102dde2dd43db9b6f5c205edf356b
work_keys_str_mv	AT yuany synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin AT wenj synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin AT tangj synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin AT kanq synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin AT ackermannr synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin AT olsenk synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin AT schwendemana synthetichighdensitylipoproteinsfordeliveryof10hydroxycamptothecin
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Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin

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