Sonoporation, drug delivery, and gene therapy

被引:121
作者
Liang, H-D [1 ,2 ]
Tang, J. [3 ]
Halliwell, M. [1 ]
机构
[1] Bristol Gen Hosp, Dept Med Phys & Bioengn, Bristol BS1 6SY, Avon, England
[2] Cardiff Univ, Sch Engn, Cardiff, S Glam, Wales
[3] Chinese Peoples Liberat Army Gen Hosp, Dept Ultrasound, Beijing, Peoples R China
关键词
diagnostic; therapeutic ultrasound; microbubble; drug delivery; gene therapy; transfection; sonoporation; targeting; INTENSITY FOCUSED ULTRASOUND; BLOOD-BRAIN-BARRIER; TARGETED MICROBUBBLE DESTRUCTION; PHOSPHOLIPIDS-BASED MICROBUBBLES; LOW-FREQUENCY SONOPHORESIS; GAS-FILLED MICROBUBBLES; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; CONTRAST AGENT; PLASMID DNA;
D O I
10.1243/09544119JEIM565
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Ultrasound is a very effective modality for drug delivery and gene therapy because energy that is non-invasively transmitted through the skin can be focused deeply into the human body in a specific location and employed to release drugs at that site. Ultrasound cavitation, enhanced by injected microbubbles, perturbs cell membrane Structures to cause sonoporation and increases the permeability to bioactive materials. Cavitation events also increase the rate of drug transport in general by augmenting the slow diffusion process with convective transport processes. Drugs and genes can be incorporated into microbubbles, which in turn can target a specific disease site using ligands Such as the antibody. Drugs can be released ultrasonically from microbubbles that are sufficiently robust to circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Local drug delivery ensures sufficient drug Concentration at the diseased region while limiting toxicity for healthy tissues. Ultrasound-mediated gene delivery has been applied to heart, blood vessel, lung, kidney, muscle, brain, and tumour with enhanced gene transfection efficiency, which depends on the ultrasonic parameters Such as acoustic pressure, Pulse length, duty cycle, repetition rate, and exposure duration, as well as microbubble properties such as size, gas species, shell material, interfacial tension, and surface rigidity. Microbubble-augmented sonothrombolysis can be enhanced further by using targeting microbubbles.
引用
收藏
页码:343 / 361
页数:19
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