Mixed micelles
View Patent ↗This disclosure is directed to mixed micelle compositions for administration of e.g., therapeutic agents or imaging agents to a subject.
1. A mixed micelle comprising a poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) molecule and a poly(ethylene oxide) 100 -polypropylene oxide 65 -poly(ethylene oxide) 100 (PEO 100 -PPO 65 -PEO 100 ) molecule, wherein the ratio of PEO-PHB-PEO to PEO 100 -PPO 65 -PEO 100 is about 7:3, wherein the mixed micelle composition further comprises an agent selected from the group consisting of a therapeutic agent and an imaging agent, and wherein PEO-PHB-PEO is synthesized from poly[(R)-3-hydroxybutyrate]diol with a molecular weight of 2,300 Da and methoxy-poly(ethylene glycol) monocarboxylic acid having a molecular weight of 4,900 Da.
2. The mixed micelle of claim 1 , wherein the agent is a therapeutic agent.
3. The mixed micelle of claim 2 , wherein the therapeutic agent is a chemotherapeutic agent.
4. The mixed micelle of claim 3 , wherein the chemotherapeutic agent is a member selected from the group consisting of doxorubicin, paclitaxel, docetaxel, actinomycin D, daunorubicin, valrubicin, idarubicin, epirubicin, bleomycin, plicamycin, camptothecin and derivatives, bleomycin, etoposide, teniposide, mitomycin, vinca alkaloids, and platinum-based compounds.
5. The mixed micelle of claim 2 , wherein the therapeutic agent is a member selected from the group consisting of analgesics, anesthetics, anti-arthritic drugs, disease modifying anti-rheumatic drugs (DMARDS), anti-asthma drugs, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antipsychotics, antihypertensives, antibiotics, antihistamines, decongestants, anti-inflammatories, muscle relaxants, anti-parasitic drugs, antiviral drugs, anti-restenotic agents, anti-spasm agents, chondroprotective agents, anti-adhesion agents, anti-tumor cell invasion agents, vasorelaxants, vasoconstrictors, immunosupressants, peptides, proteins, cytokines, growth factors, angiogenesis factors, antibodies and fragments thereof, human recombinant proteins, antigens, antisense RNA, and siRNA molecules.
6. The mixed micelle of claim 1 , wherein the agent is an imaging agent.
7. The mixed micelle of claim 6 , wherein the imaging agent is a member selected from the group consisting of indocyanine green (ICG), paramagnetic metals, iron oxide nanoparticles, quantum dots, iodine and barium.
8. The mixed micelle of claim 1 , wherein the size of the mixed micelle is about 110 nm.
9. The mixed micelle of claim 1 , wherein the mixed micelle is a filamentous micelle.
10. A pharmaceutical composition comprising a mixed micelle of claim 1 .
11. A method of making a mixed micelle comprising a poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) molecule and a poly(ethylene oxide) 100 -poly(propylene oxide 65 -poly(ethylene oxide) 100 (PEO 100 -PPO 65 -PEO 100 ) molecule, the method comprising the steps of combining the PEO-PHB-PEO and PEO 100 -PPO 65 -PEO 100 molecules and allowing the mixed micelles to form, and then encapsulating an agent selected from the group consisting of an imaging agent and a therapeutic agent within the mixed micelles, wherein the ratio of PEO-PHB-PEO to PEO 100 -PPO 65 -PEO 100 is about 7:3, and wherein PEO-PHB-PEO is synthesized from poly[(R)-3-hydroxybutyrate]diol with a molecular weight of 2,300 Da and methoxy-poly(ethylene glycol) monocarboxylic acid having a molecular weight of 4,900 Da.
12. The method of claim 11 , wherein the agent is an imaging agent.
13. The method of claim 12 , wherein the imaging agent is a member selected from the group consisting of indocyanine green (ICG), paramagnetic metals such as gadolinium or manganese, iron oxide nanoparticles, quantum dots, and heavy elements such as iodine or barium.
14. The method of claim 13 , wherein the imaging agent is indocyanine green (ICG).
15. The method of claim 11 , wherein the therapeutic agent is a chemotherapeutic agent.
16. The method of claim 15 , wherein the chemotherapeutic agent is a member of the group consisting of an antibody, a protein, a peptide, an anti-sense molecule, a small inhibitory RNA (siRNA) molecule, and a small molecule.
17. The method of claim 15 , wherein the chemotherapeutic agent is selected from the group consisting of doxorubicin, paclitaxel, docetaxel, actinomycin D, daunorubicin, valrubicin, idarubicin, epirubicin, bleomycin, plicamycin, camptothecin and derivatives, bleomycin, etoposide, teniposide, mitomycin, vinca alkaloids, and platinum-based compounds.
18. The method of claim 17 , wherein the chemotherapeutic is doxorubicin.
19. The method of claim 11 , wherein the size of the mixed micelle is about 110 nm.
20. The method of claim 11 , wherein the mixed micelle is a filamentous micelle.
21. The method of claim 11 , further comprising the step of adding the mixed micelle to a pharmaceutical carrier.