A total delivery system of genetically engineered drugs or cells for diseased vessels. Concept, materials, and fabricated prototype device.
The development of a percutaneous procedure using a catheterized system for diseased vessels has been increasingly in demand in conjunction with gene therapy using genetically engineered drugs (antisense) and cells. The authors' strategic concept realizes revascularization at narrowed, diseased sites and delivery of drugs or cells into the diseased tissues or targeted cells. An inflatable, drug-releasing double balloon is installed at the tip of a catheter. The outer balloon, fabricated with micropores (diameters of 20 and 30 mm) by an excimer laser ablation technique, releases a viscous solution containing a photoreactive polymer and drug or cells on inflation of the inner balloon. A photoresponsive water-soluble polymer, molecularly designed for its ability to achieve prolonged local residency of antisense DNA at the tissue level and enhanced transmembrane transport at the cellular level, is premixed with antisense oligonucleotide drug. On light irradiation, the nonionic polymer is reversibly converted to a positively charged polymer that can be complexed with highly negatively charged antisense DNA (c-myb), which may enhance the transmembrane delivery of antisense. On cessation of irradiation, the complex slowly dissociates to function intracellularly as an antisense drug, resulting in inhibition of cell proliferation. Thus, our integrated, dual-function balloon system may contribute to mechanical dilatation gene therapies at diseased vessels.
Kito
H
H
Department of Bioengineering, National Cardiovascular Center Research Institute, Osaka, Japan.
Suzuki
T
T
Nagahara
S
S
Nakayama
Y
Y
Tsutsui
Y
Y
Isutsui
N
N
Nakajima
N
N
Matsuda
T
T
D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D001483:Base Sequence; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005069:Evaluation Studies as Topic; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D009857:Oncogenes
D016376:Oligonucleotides, Antisense