Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin.

Content Provider	Europe PMC
Author	Jiang, Sai-Ping He, Sai-Nan Li, Yun-Long Feng, Da-Lin Lu, Xiao-Yang Du, Yong-Zhong Yu, He-Yong Hu, Fu-Qiang Yuan, Hong
Copyright Year	2013
Abstract	PurposeSafe and effective lipid nanoemulsion (LNE) formulations for the antitumor delivery of doxorubicin is designed.MethodsLNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEG)ylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated. Based on in-vitro cytotoxicity and cellular uptake tests of A549 (human lung carcinoma) cells, in-vivo biodistribution, antitumor activity, and cardiac toxicity are further examined using nude mouse bearing A549 tumor.ResultsThe LNE size decreases from 126.4 ± 8.7 nm to 44.5 ± 9.3 nm with increased weight ratio of medium-chain triglyceride to soybean oil from 1:4 to 3:2, whereas the encapsulation efficiency of doxorubicin is slightly reduced from 79.2% ± 2.1% to 71.2% ± 2.9%. The PEGylation of LNE by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(PEG)2000] (DSPE-PEG 2000) does not significantly change the size and drug encapsulation efficiency. Three-month storage at room temperature and lyophilization process does not affect the drug encapsulation efficiency, whereas the size slightly increases to almost 100 nm. The in-vitro drug-release profiles of LNEs suggest that the present formulation can prolong drug release for 48 hours. LNEs can be internalized into tumor cells in vitro and efficiently accumulate in tumor tissues in vivo by passive targeting. Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced.ConclusionThe present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin.
ISSN	11769114
Journal	International Journal of Nanomedicine
Volume Number	8
PubMed Central reference number	PMC3753155
PubMed reference number	23990722
e-ISSN	11782013
DOI	10.2147/ijn.s47708
Language	English
Publisher	Dove Medical Press
Publisher Date	2013-08-19
Access Restriction	Open
Rights License	The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Ltd, provided the work is properly attributed. © 2013 Jiang et al. This work is published by Dove Medical Press Ltd, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License
Subject Keyword	PEGylation stability antitumor activity
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Organic Chemistry Drug Discovery Medicine Biomaterials Biophysics Bioengineering Pharmaceutical Science