Polymer lung surfactants
Disclosed herein are fully synthetic polymer-based lung surfactant materials, for the first time, as next generation SRT. In vitro studies on these polymer lung surfactants show that the candidate materials effectively mimic the surface tension controlling properties of currently marketed natural lung surfactants. Further, the polymer lung surfactants have strong protein resistance, which makes this class of materials promising also for potential use in Acute Respiratory Distress Syndrome (ARDS) treatment.
1. A method of treating a pulmonary disorder of a mammal caused by deficiency and/or deactivation of functional lung surfactant in said mammal, the method comprising:
administering to said mammal a therapeutically effective amount of a polymer lung surfactant composition, wherein the polymer lung surfactant composition comprises a synthetic biocompatible amphiphilic block copolymer, wherein the hydrophilic (water soluble) block comprises a monomer selected from the group consisting of ethylene glycol (EG), ethylene oxide (EC), vinyl alcohol (VA), and oxazoline (OZ), wherein the hydrophobic (water-insoluble) block copolymer comprises a monomer selected from the group consisting of lactic acid or lactide (LA), glycolic acid or glycolide (GA), caprolactone (CL), styrene (S), methacrylate (MA), acrylate (Ac), butadiene (BD), and isoprene (IP), and wherein said polymer lung surfactant composition forms stable micelles in aqueous solution, wherein the micelles are used in uncomplexed form not loaded with any other therapeutic agents.
2. The method of claim 1 , wherein said pulmonary disorder is a neonatal respiratory distress syndrome (NRDS) or acute respiratory distress syndrome (ARDS) caused by deficiency and/or deactivation of functional lung surfactant.
3. The method of claim 1 , wherein the block copolymer lung surfactant composition comprises at least one polymerized hydrophobic block comprising methacrylate and at least one polymerized hydrophilic block comprising ethylene glycol.
4. The method of claim 1 , wherein the block copolymer lung surfactant composition comprises at least one polymerized hydrophobic block comprising lactic acid or lactide and at least one polymerized hydrophilic block comprising ethylene glycol.
5. The method of claim 1 , wherein the block copolymer lung surfactant composition comprises at least one polymerized hydrophobic block comprising butadiene and at least one polymerized hydrophilic block comprising ethylene glycol.
6. The method of claim 1 , wherein the therapeutically effective amount of the polymer lung surfactant composition is administered to the lungs of said mammal in the form of an aqueous solution via endotracheal instillation.
7. The method of claim 1 , wherein the therapeutically effective amount of the polymer lung surfactant composition is administered to the lungs of said mammal in the form of liquid drop or lyophilized powder-type aerosols through application of continuous positive airway pressure or mechanical ventilation.
8. The method of claim 7 , wherein the therapeutically effective amount of the polymer lung surfactant composition is administered to the lung in combination with other therapeutics, wherein said other therapeutics are not loaded within or do not form complexes with micelles formed by said polymer lung surfactant.