关键词: 反义寡核苷酸, 脂质体, 耐甲氧西林金黄色葡萄球菌, 耐药性

Abstract: AIM: This study was using man-made dipalmitoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol to prepare antisense oligodeoxynucleotide (AsON)anionic liposomes and to investigate the inhibitory effect of an antisense phosphothioate oligodeoxynucleotides(AS-ODNs)liposome targeting BlaR1 mRNA in methicillin-resistant Staphylococcus aureus (MRSA).METHODS: Designed and synthesized AS-ODNs by software. Prepare liposome by thin film-dispersion ,lyophilized technique.The appearances of liposomes were observed by transmission electron microscope.The liposomes were purified by centrifuge.The encapsulation efficiencies and the leaking efficiencies were determined by UV methods.The release properties in vitro were determined by agitation in PBS.The total colony forming unit(CFU)was counted.The bacteria growth curve was drawn by microplate reader.RESULTS: The liposomes were in spherical shape with uniform size.The encapsulation efficiency was 77.38 %and the leaking efficiency was 0.18 % after 1 month in lyophilized condition.The liposomes released 60 % drug after 24h when incubated in PBS with mild agitation.The AS-ODNs liposome could significantly inhibit the growth of MRSA compared with control groupand those AS-ODNs didn't encapsulated in liposome.Liposome encapsulated different concentration AS-ODNs could significantly decrease the CFU of MRSA ,which showed a concentration dependent manner (p<0.05), while AS-ODNs without liposome didn't show this effect.CONCLUSION: The liposomes prepared by this method were stable with a high encapsulation efficiency.The AS-ODNs liposome could reverse the antibiotic resistant in MRSA.The effect was better than those ASODNs without liposomes.This liposome could be used as a delivery system for AS-ODNs entrapped to bacteria.

Key words: antisense phosphothioate oligodeoxynucleotides, liposome, methicillin-resistant Staphylococcus aureus, drug-resistant