Micelle encapsulation of therapeutic agents
First Claim
1. A composition comprising micelles encapsulating three drugs,wherein the micelles comprise poly(ethylene glycol)-block-poly(lactic acid) polymers;
- the hydrophobic poly(lactic acid) block of the polymers orient toward the interior of each micelle, and the hydrophilic poly(ethylene glycol) block of the polymers orient toward the exterior of each micelle;
the molecular weight of the poly(ethylene glycol) block is about 1,000 to about 35,000 g/mol and the molecular weight of the poly(lactic acid) block is about 1,000 to about 15,000 g/mol;
the drug loading of the micelles is about 1 wt. % to about 50 wt. % with respect to the mass of the micelles;
the three drugs are non-covalently encapsulated in the interior of the micelles;
the three drugs are paclitaxel, 17-AAG, and rapamycin;
docetaxel, 17-AAG, and rapamycin;
or paclitaxel, etoposide, and 17-AAG; and
the composition is substantially free of ethanol, dimethyl sulfoxide, castor oil, and castor oil derivatives.
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Accused Products
Abstract
The invention provides active agents, such as paclitaxel, rapamycin, or 17-AAG, encapsulated by safe poly(ethylene glycol)-block-poly(lactic acid) (“PEG-b-PLA”) micelles. The compositions provide effective solubilization of drug combinations, such as paclitaxel, rapamycin, and 17-AAG, as well as others described herein. A significant advantage of PEG-b-PLA as a carrier is that it is less toxic than Cremophor® EL or DMSO, which are used in currently known compositions. Additionally, PEG-b-PLA micelles are easier to handle than DMSO and they do not possess a foul odor, which is a problem with formulations currently in clinical trials. Accordingly, the invention provides stable and biocompatible drug formulations that improve bioavailabilty without causing toxicity. It was also found that larger doses of individual drugs in micelle formulations can be administered compared to non-micelle formulations.
30 Citations
22 Claims
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1. A composition comprising micelles encapsulating three drugs,
wherein the micelles comprise poly(ethylene glycol)-block-poly(lactic acid) polymers; -
the hydrophobic poly(lactic acid) block of the polymers orient toward the interior of each micelle, and the hydrophilic poly(ethylene glycol) block of the polymers orient toward the exterior of each micelle; the molecular weight of the poly(ethylene glycol) block is about 1,000 to about 35,000 g/mol and the molecular weight of the poly(lactic acid) block is about 1,000 to about 15,000 g/mol; the drug loading of the micelles is about 1 wt. % to about 50 wt. % with respect to the mass of the micelles; the three drugs are non-covalently encapsulated in the interior of the micelles; the three drugs are paclitaxel, 17-AAG, and rapamycin;
docetaxel, 17-AAG, and rapamycin;
or paclitaxel, etoposide, and 17-AAG; andthe composition is substantially free of ethanol, dimethyl sulfoxide, castor oil, and castor oil derivatives. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A composition comprising micelles encapsulating three drugs, wherein the micelles are poly(ethylene glycol)-block-poly(lactic acid) polymers;
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the hydrophobic poly(lactic acid) block of the polymers orient toward the interior of each micelle, and the hydrophilic poly(ethylene glycol) block of the polymers orient toward the exterior of each micelle; the molecular weight of the poly(ethylene glycol) block is about 1,000 to about 35,000 g/mol and the molecular weight of the poly(lactic acid) block is about 1,000 to about 15,000 g/mol; the drug loading of the micelles is about 5 wt. % to about 50 wt. % with respect to the mass of the micelles; the three drugs are paclitaxel, 17-AAG, and rapamycin; and the composition comprises less than about 0.1 wt. % of ethanol, dimethyl sulfoxide, castor oil, and castor oil derivatives.
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21. A composition comprising micelles encapsulating three drugs, wherein the micelles are poly(ethylene glycol)-block-poly(lactic acid) polymers;
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the hydrophobic poly(lactic acid) block of the polymers orient toward the interior of each micelle, and the hydrophilic poly(ethylene glycol) block of the polymers orient toward the exterior of each micelle; the molecular weight of the poly(ethylene glycol) block is about 1,000 to about 35,000 g/mol and the molecular weight of the poly(lactic acid) block is about 1,000 to about 15,000 g/mol; the drug loading of the micelles is about 5 wt. % to about 50 wt. % with respect to the mass of the micelles; the three drugs are docetaxel, 17-AAG, and rapamycin; and the composition comprises less than about 0.1 wt. % of ethanol, dimethyl sulfoxide, castor oil, and castor oil derivatives.
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22. A composition comprising micelles encapsulating three drugs, wherein the micelles are poly(ethylene glycol)-block-poly(lactic acid) polymers;
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the hydrophobic poly(lactic acid) block of the polymers orient toward the interior of each micelle, and the hydrophilic poly(ethylene glycol) block of the polymers orient toward the exterior of each micelle; the molecular weight of the poly(ethylene glycol) block is about 1,000 to about 35,000 g/mol and the molecular weight of the poly(lactic acid) block is about 1,000 to about 15,000 g/mol; the drug loading of the micelles is about 5 wt. % to about 50 wt. % with respect to the mass of the micelles; the three drugs are paclitaxel, etoposide, and 17-AAG; and the composition comprises less than about 0.1 wt. % of ethanol, dimethyl sulfoxide, castor oil, and castor oil derivatives.
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Specification