Preparation and in vitro and in vivo study of antisense oligodeoxynucleotides-loaded cationic liposomes.
- Author:
Yang LIU
1
;
Zhen-zhong ZHANG
;
Kun LI
;
Qian MEI
Author Information
1. College of Pharmacy, Zhengzhou University, Zhengzhou 450001, China. liuyang8016@126.com
- Publication Type:Journal Article
- MeSH:
Animals;
Breast Neoplasms;
metabolism;
pathology;
Cations;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Drug Carriers;
Female;
Freeze Drying;
Humans;
Liposomes;
chemistry;
pharmacokinetics;
pharmacology;
Mice;
Mice, Inbred BALB C;
Neoplasm Transplantation;
Oligodeoxyribonucleotides, Antisense;
chemistry;
genetics;
Particle Size;
Transfection
- From:
Acta Pharmaceutica Sinica
2009;44(11):1273-1277
- CountryChina
- Language:Chinese
-
Abstract:
The aim of the paper is to prepare stable antisense oligodeoxynucleotides-loaded cationic liposomes and evaluate the transfection efficiency of asODN to MCF-7 oophoroma cells and study their distribution to different tissues in mice. Antisense oligodeoxynucleotides (asODN)-loaded cationic liposomes were prepared by a thin film-adsorption-lyophilization method which is simple and can overcome crucial pharmaceutical defects (e.g. instability) of liposomes during storage. The morphology was investigated by transmission electron microscope. The size and surface charge of the liposomes were determined by laser particle analyter. The dissociated ligodeoxynucleotides were separated from the liposomes by sephadex column and the entrapment efficiency was determined by using an ultraviolet photometer. Trehalose, mannitol, and glycine were suitable for lyophilization especially trehalose. The resulting liposomes were global microcapsule in a narrow particle size with a mean diameter of 175 nm and 320 nm before and after lyophilization, and a high zeta potentials of +32 mV. The dissociated asODN were separated from the liposomes by sephadex G-50 column and the entrapment coefficient of asODN was 88.4% pre and 83.2% post-lyophilization separately for trehalose. The growth of MCF-7 oophoroma cells were inhibited in vitro obviously (P < 0.05) and transfection efficiency of asODN was 18%, 26%, 44% after 2 h, 4 h and 8 h, respectively. The formulation and method can be used to prepare stable cationic liposomes which can effectively inhibit the growth of MCF-7 oophoroma cells and obtain a high transfection efficiency. This system can improve distribution amount of asODN to tissues especially tumors in mice.
