Nanoparticles loaded with chemotherapeutic antitumoral drug
View Patent ↗The invention relates to new therapeutic approaches for treating cancer, in particular hepatocellular carcinoma, with Nanoparticules loaded with a chemotherapeutic antitumoral agent. In particular, it relates to the treatment of cancer by administration of said Nanoparticules by intravenous infusion for at least 2 hours in order to prevent toxicological side effects and increase the benefit/risk ratio of the treatment.
1. A method for reducing, in a cancer patient, the occurrence or severity of macroscopic lung injuries induced by nanoparticles that comprise:
at least one chemotherapeutic antitumoral agent that is doxorubicin or a pharmaceutically acceptable salt thereof,
at least one poly(alkylcyanoacrylate), and
at least one cyclodextrin,
the method comprising administering the nanoparticles to the cancer patient by intravenous infusion for at least 2 hours;
wherein the macroscopic lung injuries induced by the nanoparticles occur two or more days after infusion;
wherein the dosage of doxorubicin or pharmaceutically acceptable salt thereof administered by said intravenous infusion is from about 10 to about 30 mg/m 2 .
2. The method according to claim 1 , wherein the nanoparticles are administered by intravenous infusion for between 2 and 24 hours.
3. The method according to claim 1 , wherein the nanoparticles are administered by intravenous infusion for between 4 and 12 hours.
4. The method according to claim 1 , wherein the nanoparticles are administered by intravenous infusion for about 6 hours.
5. The method according to claim 1 , wherein said at least one poly(alkylcyanoacrylate) is a poly(C 6 C 8 alkylcyanoacrylate).
6. The method according to claim 1 , wherein said at least one poly(alkylcyanoacrylate) is a polyisohexylcyanoacrylate.
7. The method according to claim 1 , wherein:
said at least one chemotherapeutic antitumoral agent is at a concentration from 0.01 to 200 mg/g of the nanoparticles,
said at least one cyclodextrin is in an amount of from 0.1% to 70% w/w of the nanoparticles, and
said at least one poly(alkylcyanoacrylate) is in an amount of from 1% to 25% w/w of the nanoparticles.
8. The method according to claim 7 , wherein said at least one chemotherapeutic antitumoral agent is at a concentration from about 1 to about 50 mg/g of the nanoparticles.
9. The method according to claim 7 , wherein said at least one cyclodextrin is in an amount of from about 1% to about 30% w/w of the nanoparticles.
10. The method according to claim 7 , wherein said at least one poly(alkylcyanoacrylate) is in an amount of from about 5% to about 15% w/w of the nanoparticles.
11. The method according to claim 1 , wherein the dosage of doxorubicin administered by said intravenous infusion is from about20 to about 30 mg/m 2 .
12. The method according to claim 1 , wherein the dosage of doxorubicin administered by said intravenous infusion is about 30 mg/m 2 .
13. The method according to claim 1 , wherein the cancer patient has a hepatocellular carcinoma.
14. The method according to claim 13 , wherein the cancer patient has an advanced hepatocellular carcinoma after failure or intolerance to sorafenib.
15. The method according to claim 1 , wherein the cancer patient has a solid tumor.
16. The method according to claim 1 , wherein the cancer patient has a hematopoietic tumor.
17. The method according to claim 1 , wherein the macroscopic lung injuries induced by the nanoparticles are fatal or life-threatening macroscopic lung injuries.
18. A method for reducing, in a cancer patient, the occurrence or severity of macroscopic lung injuries induced by nanoparticles that comprise:
at least one chemotherapeutic antitumoral agent that is doxorubicin or a pharmaceutically acceptable salt thereof,
at least one poly(alkylcyanoacrylate), and
at least one cyclodextrin,
the method comprising administering the nanoparticles to the cancer patient by intravenous infusion for about 6 hours;
wherein the macroscopic lung injuries induced by the nanoparticles occur two or more days after infusion;
wherein the dosage of doxorubicin or pharmaceutically acceptable salt thereof administered by said intravenous infusion is from about 20 to about 30 mg/m 2 ;
wherein the cancer patient has an advanced hepatocellular carcinoma after failure or intolerance to sorafenib.
19. A method for reducing, in a cancer patient, the mortality associated with macroscopic lung injuries induced by nanoparticles that comprise:
at least one chemotherapeutic antitumoral agent that is doxorubicin or a pharmaceutically acceptable salt thereof,
at least one poly(alkylcyanoacrylate), and
at least one cyclodextrin,
the method comprising administering the nanoparticles to the cancer patient by intravenous infusion for at least 2 hours;
wherein the macroscopic lung injuries induced by the nanoparticles occurs two or more days after infusion;
wherein the dosage of doxorubicin or pharmaceutically acceptable salt thereof administered by said intravenous infusion is from about 10 to about 30 mg/m 2 .
20. A method for reducing, in a cancer patient, the occurrence of fatal respiratory distress induced by nanoparticles that comprise:
at least one chemotherapeutic antitumoral agent that is doxorubicin or a pharmaceutically acceptable salt thereof,
at least one poly(alkylcyanoacrylate), and
at least one cyclodextrin,
the method comprising administering the nanoparticles to the cancer patient by intravenous infusion for at least 2 hours;
wherein the fatal respiratory distress induced by the nanoparticles occurs two or more days after infusion;
wherein the dosage of doxorubicin or pharmaceutically acceptable salt thereof administered by said intravenous infusion is from about 10 to about 30 mg/m 2 .