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Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin

Authors Yuan Y, Wen J, Tang J, Kan Q, Ackermann R, Olsen K, Schwendeman A

Received 15 May 2016

Accepted for publication 10 September 2016

Published 22 November 2016 Volume 2016:11 Pages 6229—6238

DOI https://doi.org/10.2147/IJN.S112835

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Carlos Rinaldi


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

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