Acoustically active drug delivery systems
First Claim
1. A method for the controlled delivery of a therapeutic compound to a region of a patient comprising:
- (i) administering to a patient a targeted therapeutic delivery system comprising, in combination with a therapeutic compound, stabilized lipid microspheres encapsulating a gas or gaseous precursor and an oil, wherein said microspheres comprises at least one phosphatidylcholine, at least one phosphatidylethanolamine, and at least one phosphatidic acid, wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine dimyistoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoyl-phosphatidylcholine;
said phosphatidylethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine-PEG 5,000, dioleoyl-phosphatidylethanolamine, and N-succinyl-dioleoyl-phosphatidylethanolamine; and
said phosphatidic acid is dipalmatoylphosphatidic acid;
(ii) monitoring the targeted therapeutic delivery system using diagnostic ultrasound to determine the presence of the microspheres in said region; and
(iii) applying therapeutic ultrasound to said region to induce rupturing of said microspheres, thereby releasing the therapeutic compound in said region, wherein said therapeutic compound is encapsulated or embedded in said microspheres, and said therapeutic ultrasound is applied at a level below the threshold level for lethal cytotoxicity.
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Abstract
The present invention is directed to targeted therapeutic delivery systems comprising a gas or gaseous precursor filled microsphere wherein said gas or gaseous precursor filled microsphere comprises an oil, a surfactant, and a therapeutic compound. Methods of preparing the targeted therapeutic delivery systems are also embodied by the present invention which comprise processing a solution comprising an oil and a surfactant in the presence of a gaseous precursor, at a temperature below the gel to liquid crystalline phase transition temperature of the surfactant to form gas or gaseous precursor filled microsphere, and adding to said microspheres a therapeutic compound resulting in a targeted therapeutic delivery system, wherein said processing is selected from the group consisting of controlled agitation, controlled drying, and a combination thereof.
600 Citations
15 Claims
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1. A method for the controlled delivery of a therapeutic compound to a region of a patient comprising:
- (i) administering to a patient a targeted therapeutic delivery system comprising, in combination with a therapeutic compound, stabilized lipid microspheres encapsulating a gas or gaseous precursor and an oil, wherein said microspheres comprises at least one phosphatidylcholine, at least one phosphatidylethanolamine, and at least one phosphatidic acid, wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine dimyistoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoyl-phosphatidylcholine;
said phosphatidylethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dipalmitoylphosphatidylethanolamine-PEG 5,000, dioleoyl-phosphatidylethanolamine, and N-succinyl-dioleoyl-phosphatidylethanolamine; and
said phosphatidic acid is dipalmatoylphosphatidic acid;
(ii) monitoring the targeted therapeutic delivery system using diagnostic ultrasound to determine the presence of the microspheres in said region; and
(iii) applying therapeutic ultrasound to said region to induce rupturing of said microspheres, thereby releasing the therapeutic compound in said region, wherein said therapeutic compound is encapsulated or embedded in said microspheres, and said therapeutic ultrasound is applied at a level below the threshold level for lethal cytotoxicity. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
- (i) administering to a patient a targeted therapeutic delivery system comprising, in combination with a therapeutic compound, stabilized lipid microspheres encapsulating a gas or gaseous precursor and an oil, wherein said microspheres comprises at least one phosphatidylcholine, at least one phosphatidylethanolamine, and at least one phosphatidic acid, wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine dimyistoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoyl-phosphatidylcholine;
Specification