Hierarchical siliceous mesosilicalite nanocarrier loaded with platinum(ii) complex

Patent metadata

Field	Value
Publication number	US-2019231897-A1
Application number	US-201815992953-A
Country	US
Kind code	A1
Filing date	May 30, 2018
Priority date	Feb 1, 2018
Publication date	Aug 1, 2019
Grant date	—

Abstract

A platinum(II) complex loaded on a mesosilicalite nanocarrier having a hierarchical silicalite characterized by a molar ratio of aluminum to silica in a range of 1:3000 to 1:1000. The hierarchical silicalite includes mesopores of a hexagonal structure, and micropores of silicalite structure with a microporous volume in the range of 0.05 cc/g to 0.1 cc/g. The mesosiliclite nanocarrier loaded with the platinum(II) complex is suitable for treatment of cancer, in particular, breast, cervical, and colon cancers.

First claim

1 : A mesosilicalite nanocarrier, comprising:
a hierarchical silicalite having a silica to aluminum molar ratio in a range of 1000:1 to 3000:1, comprising:
a mesophase with mesopores of a hexagonal structure; and
a microphase with micropores of a microporous volume in the range of 0.05 cc/g to 0.1 cc/g; and
a platinum(II) complex loaded in the mesopores and micropores of the nanocarrier;
wherein a mean pore diameter of the mesosilicalite nanocarrier is in the range of 1.5 nm to 5.5 nm.

2 : The mesosilicalite nanocarrier of claim 1 , wherein the platinum(II) complex is at least one selected from the group consisting of cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, and strataplatin.

3 : The mesosilicalite nanocarrier of claim 1 , wherein the platinum(II) is present in amount in the range of 0.001 to 1800 mmol/g of the total weight of the mesosilicalite nanocarrier.

4 : The mesosilicalite nanocarrier of claim 1 , wherein the platinum(II) is present in amount in the range of 0.01 to 0.9 mmol/g of the total weight of the mesosilicalite nanocarrier.

5 : The mesosilicalite nanocarrier of claim 1 , wherein mesosilicalite nanocarrier comprises a first group of pores having a pore diameter in the range of about 2.1 to 3.0 nm and a second group of pores having a pore diameter in the range of about 3.4 to 4.0 nm.

6 : The mesosilicalite nanocarrier of claim 1 , wherein the mesosilicalite nanocarrier has a surface area in the range of 400 to about 1400 m 2 /g.

7 : The mesosilicalite nanocarrier of claim 1 , wherein the mesosilicalite nanocarrier has a pore volume in the range of 0.30-0.90 mL/g.

8 : A method of making a mesosilicalite nanocarrier loaded with a platinum(II) complex, comprising:
mixing a hierarchical mesosilicalite nanocarrier having a silica to aluminum molar ratio in a range of 1000:1 to 3000:1 with the platinum(II) complex dissolved in a salt solution, sterring the mixture for about 16 to 40 hours, and separating the mesosilicalite nanocarrier loaded with the platinum(II) complex, wherein the mesosilicalite nanocarrier has a mean pore diameter in the range of 1.5 nm to 5.5 nm.

9 : The method of claim 8 , wherein the salt solution is 0.9% sodium chloride in water.

10 : The method of claim 8 , wherein the concentration of the platinum(II) complex in the salt solution is in the range of about 1.0 to 20.0 mM.

11 : A pharmaceutical composition comprising the mesosilicalite nanocarrier of claim 1 .

12 : The pharmaceutical composition of claim 11 , wherein the platinum(II) complex is at least one selected from the group consisting of cisplatin, carboplatin, oxaliplatin, nedaplatin, triplatin tetranitrate, phenanthriplatin, picoplatin, and strataplatin.

13 : The pharmaceutical composition of claim 11 , wherein the platinum(II) complex is cisplatin.

14 : The pharmaceutical composition of claim 11 , wherein the mesosilicalite nanocarrier loaded with the platinum(II) complex at a loading of in the range of about 0.011 to mmol of 0.9 mmol of platinum(II) complex per gram of nanocarrier.

15 : The pharmaceutical composition of claim 11 , further comprising a chemotherapeutic agent.

16 : The pharmaceutical composition of claim 11 , further comprising one or more carriers and/or excipients selected from the group consisting of a buffer, an inorganic salt, a fatty acid, a vegetable oil, a synthetic fatty ester, a surfactant, a sugar, a polymer, and combinations thereof.

17 : A method for treating a proliferative disorder, comprising:
administering to a subject in need of therapy an effective amount of the pharmaceutical composition of claim 11 .

18 : The method of claim 17 , wherein the proliferative disorder is a cancer selected from the group consisting of ovarian cancer, cervical cancer, testicular cancer, colon cancer, bladder cancer, breast cancer, non-small cell lung cancer, esophageal cancer, endometrial cancer, head and neck cancer, and an osteogenic sarcoma.

19 : The method of claim 17 , wherein the proliferative disorder is a tumor.

20 : The method of claim 17 , wherein the subject is a mammal.

Assignees

• Univ Imam Abdulrahman Bin Faisal

Inventors

• Balasamy Rabindran Jermy
• Acharya Sadananda
• Ravinayagam Vijaya

Classifications

• A61K9/5115

  Inorganic compounds · CPC title

• A61K31/282

  Platinum compounds · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K47/6923 Primary

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title

• A61P35/00

  Antineoplastic agents · CPC title