Stable microspheres, method off abrication and use thereof
AssigneeB.G. Negev Technologies and Applications Ltd., At Ben-Gurion University
InventorsShani Tsirkin, Joseph Kost, Tamar Traitel, Riki Goldbart
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Abstract
Stable and durable polymeric microbubbles of a 1-10 μm size range are disclosed. The microbubbles are synthesized from the co-polymer poly lactic-co-glycolic acid (PLGA), which provides a plurality of PLGA microbubbles presenting diverse cavitation activities. The PLGA microbubbles are particularly suitable for cavitation enhancement purposes and are applicable in various clinical procedures such as ablation or enhancement of uptake of chemical or biological therapy in cells and tissue.
Claims21
A plurality of microbubbles comprising a polymeric shell encapsulating a gas, wherein at least a portion of the microbubbles are hollow, single-core microbubbles of 10 μm diameter or less, comprising a non-porous poly-lactic-co-glycolic acid copolymer (PLGA) shell of a predetermined lactic acid:glycolic acid molar ratio, and thickness of from about 100 nm to about 800 nm, and wherein the plurality of microbubbles are produced by a double emulsion solvent evaporation method comprising the steps of:
- (i) obtaining an organic phase (O) comprising the PLGA copolymer in an amount of from about 10 mg/ml to about 100 mg/ml, and an organic solvent;
- (ii) obtaining a first aqueous phase (W1) comprising a first surfactant in an amount in a range of from about 0.1% w/v to about 15.0% w/v;
- (iii) obtaining a second aqueous phase (W2) comprising a second surfactant in an amount in a range of from about 2% w/v to about 15% w/v;
- (iv) combining the organic phase and the first aqueous phase under emulsification conditions to obtain a first microemulsion W1/O, having a W1:O volume ratio in the range of from about 0.5:10.0 to about 5.0:10.0;
- (v) combining a portion of the first microemulsion W1/O with the second aqueous phase under emulsification conditions to obtain a second microemulsion W1/O/W2;
- (vi) evaporating the organic solvent;
- and
- (vii) harvesting the microbubbles, washing and, optionally, subjecting them to lyophilization.
A plurality of microbubbles comprising a polymeric shell encapsulating a gas, wherein at least a portion of the microbubbles comprise a poly-lactic-co-glycolic acid copolymer (PLGA) shell of a predetermined lactic acid:glycolic acid ratio, the plurality of microbubbles are produced by a double emulsion process comprising the steps of:
- (i) obtaining an organic phase (O) comprising the PLGA copolymer and an organic solvent;
- (ii) obtaining a first aqueous phase (W1) comprising partially hydrolyzed polyvinyl alcohol (PVA) in an amount of from about 0.1% w/v to about 15.0% w/v and molecular weight of from about 10 kDa to about 200 kDa;
- (iii) obtaining a second aqueous phase (W2) comprising partially hydrolyzed PVA in an amount of from about 0.5% w/v to about 15.0% w/v and molecular weight of from about 10 kDa to about 200 kDa;
- (iv) combining the organic phase and the first aqueous phase under emulsification conditions to obtain a first microemulsion W1/O, having a W1:O volume ratio of from about 0.5:10.0 to about 5.0:10.0;
- (v) combining a portion of the first microemulsion W1/O with the second aqueous phase under emulsification conditions to obtain a second microemulsion W1/O/W2;
- (vi) evaporating the organic solvent;
- and
- (vii) harvesting the microbubbles, washing and, optionally, subjecting them to lyophilization.
Dependencies are inferred from the claim text.