Title |
Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin
|
---|---|
Published in |
International Journal of Nanomedicine, November 2016
|
DOI | 10.2147/ijn.s112835 |
Pubmed ID | |
Authors |
Yue Yuan, Jian Wen, Jie Tang, Qiming Kan, Rose Ackermann, Karl Olsen, Anna Schwendeman |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 20 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 5 | 25% |
Student > Doctoral Student | 2 | 10% |
Professor > Associate Professor | 2 | 10% |
Student > Ph. D. Student | 1 | 5% |
Other | 1 | 5% |
Other | 2 | 10% |
Unknown | 7 | 35% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 25% |
Chemistry | 3 | 15% |
Chemical Engineering | 2 | 10% |
Medicine and Dentistry | 2 | 10% |
Biochemistry, Genetics and Molecular Biology | 1 | 5% |
Other | 1 | 5% |
Unknown | 6 | 30% |