PH responsive drug conjugated nanocarriers
The presently disclosed invention relates to products and methods of treating cancer in a patient comprising administering to the patient a pharmaceutically therapeutic dose of a chemotherapeutic, or any pharmaceutically acceptable salt, solvate, or prodrug thereof, conjugated to a nanocarrier. According to a further embodiment, the chemotherapeutic has a primary (1°) amine (—NH 2 ) group in within a pharmaceutical structure of the chemotherapeutic structure. According to a further embodiment, the chemotherapeutic is one of a platinum-based pharmaceutical and an Anthracycline family pharmaceutical. According to a further embodiment, the chemotherapeutic is one of gemcitabine, methotrexate, cisplatin, oxaliplatin, doxorubicin, daunorubicine, idarubicine, and epirubicine. According to a further embodiment, the chemotherapeutic is either attached to the nanocarrier by means that includes covalent bonds or is attached by means that does not included covalent bonds. According to a further embodiment, the nanocarrier is a pH-sensitive nanocarrier.
1. A pharmaceutical composition comprising a chemotherapeutic, or any pharmaceutically acceptable salt, solvate, or prodrug thereof, covalently conjugated to a poly(ethylene glycol)-b-poly(carbonate) (PEG-PC) block copolymer nanocarrier;
wherein the chemotherapeutic has a primary (1°) amine (—NH2) group within a pharmaceutical structure of the chemotherapeutic structure.
2. The pharmaceutical composition of claim 1 wherein the chemotherapeutic is one of gemcitabine, methotrexate, doxorubicin, daunorubicine, idarubicine, and epirubicine.
3. The pharmaceutical composition of claim 1 wherein the nanocarrier contains a 2-pyrrolidine-1-yl-ethyl-amine and a polycarbonate.
4. The pharmaceutical composition of claim 1 , wherein the chemotherapeutic is doxorubicin.
5. The pharmaceutical composition of claim 1 wherein the nanocarrier is a pH-sensitive nanocarrier.
6. The pharmaceutical composition of claim 1 wherein the nanocarrier releases the chemotherapeutic substantially only in an acidic environment.
7. The pharmaceutical composition of claim 1 wherein the nanocarrier releases the chemotherapeutic preferentially at a pH of 5.5 compared to a pH of 7.4.
8. The pharmaceutical composition of claim 1 wherein the chemotherapeutic is not encapsulated.
9. The pharmaceutical composition of claim 1 wherein the chemotherapeutic nanocarrier conjugate has a positive surface charge.
10. The pharmaceutical composition of claim 1 wherein the chemotherapeutic nanocarrier conjugate has a tertiary amine trigger.
11. A pharmaceutical composition comprising:
a chemotherapeutic covalently conjugated to a pH-sensitive nanocarrier by a conditionally unstable amide bond;
wherein the chemotherapeutic is one of gemcitabine, methotrexate, cisplatin, oxaliplatin, doxorubicin, daunorubicine, idarubivine, and epirubicine, or any pharmaceutically acceptable salt, solvate, or prodrug thereof, and the nanocarrier contains a 2-pyrrolidine-1-yl-ethyl-amine and a polycarbonate.
12. A pharmaceutical composition comprising a chemotherapeutic, or any pharmaceutically acceptable salt, solvate, or prodrug thereof, covalently conjugated to a poly(ethylene glycol)-b-poly(carbonate) (PEG-PC) block copolymer nanocarrier by a conditionally unstable amide bond.