Micelle encapsulation of a combination of therapeutic agents
First Claim
1. A composition comprising micelles encapsulating three drugs, whereinthe three drugs are non-covalently encapsulated in the interior of the micelles;
- the micelles comprise poly(ethylene glycol)-block-poly(lactic acid) polymers where 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;
a first drug of the three drugs encapsulated in the micelles is 17-AAG or 17-DMAG;
a second drug of the three drugs encapsulated in the micelles is paclitaxel or docetaxel; and
a third drug of the three drugs encapsulated in the micelles is rapamycin, deforolimus, temsirolimus, everolimus, etoposide, or teniposide.
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Accused Products
Abstract
The invention provides active agents, such as paclitaxel, rapamycin, or 17-DMAG, 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-DMAG, 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 bioavailability without causing toxicity. It was also found that larger doses of individual drugs in micelle formulations can be administered compared to non-micelle formulations.
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Citations
22 Claims
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1. A composition comprising micelles encapsulating three drugs, wherein
the three drugs are non-covalently encapsulated in the interior of the micelles; -
the micelles comprise poly(ethylene glycol)-block-poly(lactic acid) polymers where 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; a first drug of the three drugs encapsulated in the micelles is 17-AAG or 17-DMAG; a second drug of the three drugs encapsulated in the micelles is paclitaxel or docetaxel; and a third drug of the three drugs encapsulated in the micelles is rapamycin, deforolimus, temsirolimus, everolimus, etoposide, or teniposide. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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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; a first drug of the three drugs encapsulated in the micelles is 17-AAG or 17-DMAG; a second drug of the three drugs encapsulated in the micelles is paclitaxel; a third drug of the three drugs encapsulated in the micelles is rapamycin, deforolimus, temsirolimus, everolimus, etoposide, or teniposide; the drug loading of the micelles is about 5 wt. % to about 50 wt. % with respect to the mass of the micelles; and
the composition comprises less than about 2 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; a first drug of the three drugs encapsulated in the micelles is 17-AAG or 17-DMAG; a second drug of the three drugs encapsulated in the micelles is docetaxel; a third drug of the three drugs encapsulated in the micelles is rapamycin, deforolimus, temsirolimus, everolimus, etoposide, or teniposide; the drug loading of the micelles is about 5 wt. % to about 50 wt. % with respect to the mass of the micelles; and
the composition comprises less than about 2 wt. % of ethanol, dimethyl sulfoxide, castor oil, and castor oil derivatives.
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Specification