Foam for pulmonary drug delivery

Abstract

A method for delivery of one or more active agents into the pulmonary system of a subject using liquid foam is provided. The invention further provides a pulmonary drug delivery device for providing a liquid foam to a target site of a respiratory system.

1 . A method for delivering a composition to a target site of a respiratory system of a subject, the method comprising the steps of:
 i. providing a composition comprising a liquid foam;   ii. introducing said composition to a first site of said respiratory system, wherein said first site is proximal to said target site; and optionally   iii. introducing a predefined volume of gas, into said respiratory system to push said composition from said first site into said target site of the respiratory system,   thereby delivering said composition to said target site.   
     
     
         2 . The method of  claim 1 , comprising a preliminary step of subjecting said subject to pre-oxygenation. 
     
     
         3 . The method of  claim 1 , wherein said composition is delivered to one or more target sites within the respiratory system of said subject. 
     
     
         4 . The method of  claim 3 , wherein said composition is delivered simultaneously or sequentially to each of said one or more target sites. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein said first site is selected from the group consisting of: trachea, right main bronchus, left main bronchus, right lobar (secondary) bronchi, left lobar bronchi, any one of the segmental (tertiary), any one of the conducting bronchioles, any one of the terminal bronchioles, and any combination thereof. 
     
     
         7 . The method of  claim 1 , wherein said target site is selected from (i) a site selected from the group consisting of: right lung, left lung, and a combination thereof, and (ii) a target site selected from the group consisting of: trachea bronchi of the right lung, bronchioles of the right lung, alveolar ducts of the right lung, alveoli of the right lung, alveolar sacs of the right lung, capillary of the right lung, bronchi of the left lung, bronchioles of the left lung, alveolar ducts of the left lung, alveoli of the left lung, alveolar sacs of the left lung, capillary of the left lung and any combination thereof. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein at least one of said introduction of steps (ii) and (iii) is performed in a controllable manner, and/or by using a device selected from the group consisting of: bronchoscope, a catheter, a tube, a nasotracheal tube, and an orthotracheal tube. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein said composition is delivered to said respiratory system in a rate of 3 to 9 liter per min. 
     
     
         12 . The method of  claim 1 , wherein said liquid foam is transformed into liquid within a predefined time range, optionally wherein the predefined time range is 1 second to 60 minutes within said target site. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein said foam has a half-life of 0.5 seconds to 30 minutes within said target site, under any one of (i) a temperature range of 35 to 40 degrees Celsius, and (ii) under a pressure in the range of 50 to −20 cmH 2 O gage. 
     
     
         15 .- 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein a transformation or breakdown of said liquid foam into liquid is induced by at least one method selected from the group consisting of: acoustic waves, and high frequency oscillatory ventilation (HFOV), or by a method comprising the step of: contacting said composition with a predefined volume of gas comprising a de-foaming agent to induce breakdown of said liquid foam. 
     
     
         18 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein said liquid foam is selected from (i) a liquid foam having a viscosity ranges between 0.01 to 1 Pa·s; (ii) a liquid foam comprising gas bubbles having an average diameter size of 5 μm to 5 mm. 
     
     
         21 . The method  claim 1 , wherein a liquid constitutes between 2% to 30% of said liquid foam. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein said composition further comprises one or more active agents, wherein any one of (i) said one or more active agents constitute between 0.01% to 100% of a liquid fraction of said foam; (ii) one or more active agents are selected from the group consisting of: therapeutic agent, prophylactic agent and diagnostic agent; and (iii) one or more active agents selected from the group consisting of: a protein, a peptide, a nucleic acid, a small molecule, a lipid, a glycolipid, a cell, and an antibody; (iv) one or more active agents selected from the group consisting of: a surfactant, a cytotoxic agent, an antineoplastic agent, a chemotherapeutic agent, anti-metastatic agent, a hormone, a steroid, a bronchodilator, an anticoagulant, an immune-modulating agent, a β-agonist, an antibiotic, anti-fungal agent, anti-bacterial and an antiviral agent. 
     
     
         24 .- 27 . (canceled) 
     
     
         28 . The method of  claim 1 , further comprising a step of pulling back at least partial amount of said liquid foam from said target site of the respiratory system. 
     
     
         29 . A pulmonary drug delivery device configured to provide a liquid foam to a target site of a respiratory system of a subject. 
     
     
         30 . The pulmonary drug delivery device of  claim 29 , comprising:
 a first compartment configured to provide a liquid foam; and   an elongated hollow tube having (i) a proximal end configured to receive said liquid foam, so that the liquid foam is pushed therein; and (ii) a distal end configured to insert said foam into said target site of the respiratory system of said subject.   
     
     
         31 . The pulmonary drug delivery device of  claim 30 , further comprising a second compartment configured to provide a pressurized gas, wherein said gas pushes said liquid foam into the target site of the respiratory system. 
     
     
         32 . The pulmonary drug delivery device of  claim 30 , wherein any one of: (i) an outlet of said first compartment is sized and shaped to attach to a proximal site of the target site of the respiratory system; (ii) said first compartment further comprises an agitation element; (iii) said second compartment is selected from the group consisting of: syringe and a ventilation machine: (iv) wherein said distal end is sized and shaped to attach to said respiratory system of said subject, so that the liquid foam is directly injected to said respiratory system; (v) wherein said liquid foam further comprises or has incorporated thereto a surfactant; (vi) wherein said liquid foam further comprises or has incorporated thereto, one or more active agents, (vii) wherein said liquid foam further comprises or has incorporated thereto, one or more active agents selected from the group consisting of: stem cells, and proteins. 
     
     
         33 . The pulmonary drug delivery device of  claim 29  further comprising a control unit adapted to control one or more parameters selected from the group consisting of: a flow rate of said liquid foam in said elongated hollow tube, and the amount of said liquid foam inserted into said respiratory system. 
     
     
         34 .- 45 . (canceled)