Method for pressure mediated selective delivery of therapeutic substances and cannula

A method of determining a threshold pressure for selective administration of a therapeutic or diagnostic substance, the method comprising:

• isolating a hollow organ space;
• one or more times, introducing a test fluid into the hollow organ space at a preselected flow rate;
• and
• one or more times, administering a test solution to determine a pressure at which leakage across epithelial or endothelial tight junctions occurs;
• and
• administering a liquid including the therapeutic or diagnostic substance by introducing the liquid into the isolated hollow organ space, during which the pressure is not exceeded with the purpose of preferentially delivering the substance to an epithelial layer of the hollow organ space, or during which the peak pressure is exceeded with the purpose of preferentially delivering the substance to a subepithelial layer of the hollow organ space.

A method of determining the delivery pressure for selective administration of a therapeutic or diagnostic substance, the method comprising:

• isolating a hollow organ space;
• one or more times, introducing a test fluid into the hollow organ space at a preselected approximately constant pressure;
• one or more times, measuring the infusion rate of the administered fluid as the test fluid is introduced;
• and
• administering a liquid including a test solution into the hollow organ space and determining a flow rate at which paracellular leakage across endothelial or epithelial tight junctions occurs.

A method of accessing an interior of a gall bladder, the method comprising:

• inserting a trochar into a cannula having first and second peripheral inflatable cuffs;
• introducing the trochar, together with the cannula, at an insertion site through the wall of the gall bladder and advancing the cannula into the gall bladder such that the first inflatable cuff enters the gall bladder but the second inflatable cuff does not;
• inflating the first cuff so that it abuts an inner face of the gall bladder around the insertion site;
• and
• inflating the second cuff so that it abuts an outer face of the gall bladder around the insertion site.

A method of delivering a therapeutic or diagnostic agent to a selected portion of the liver, the method comprising:

• introducing a catheter into a hepatic duct draining the selected portion of the liver;
• occluding the duct normograde from a distal tip of the catheter;
• and
• infusing the therapeutic or diagnostic agent through the catheter into at least a portion of the selected portion of the liver at a preselected pressure that has been determined to move the agent out of the duct and into the periductular tissue.