Method for making a conjugate azole-based surface modified silicon dioxide nanoparticle

Patent metadata

Field	Value
Publication number	US-11564994-B2
Application number	US-202117308139-A
Country	US
Kind code	B2
Filing date	May 5, 2021
Priority date	Apr 10, 2019
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

A combination therapy involving different therapeutic molecules can enhance and improve the therapeutic potentials. An effective therapeutic strategy conjugates silica (SiO 2 ) nanoparticles with, e.g., 3-glycidyloxypropyl, trimethoxysilane and azoles, e.g., 1,2,4-triazole (Tri), 3-aminotriazole (ATri), 5-aminetetrazole (Atet), imidazole (Imi). These exemplary materials—classified as SiO 2 -3GPS-Tri (Conj. 1), SiO 2 -3GPS-Atri (Conj. 2), SiO 2 -3GPS-Atet (Conj. 3), SiO 2 -3GPS-Btri (Conj. 4), and SiO 2 -3GPS-Imi (Conj. 5)—can amplify targeting of therapeutics for human colorectal carcinoma cells (HCT-116), enhancing anti-cancer effects.

First claim

The invention claimed is:

1. A method of preparing a conjugate composition, comprising:
reacting a linker of Formula (1)
(C 1-5 O—) 3 —Si—C 2-10 —O—C 1-10 -oxirane  (1),

with an azole, to obtain a first product;
mixing the first product with silicon dioxide nanoparticles to obtain a mixture, wherein the silicon dioxide nanoparticles have an average diameter in a range of from 5 to 60 nm and a silicon dioxide content of at least 75 wt. %, relative to a total nanoparticle weight; and
heating the mixture at a temperature in a range of from 50 to 90° C. to form the conjugate composition,
wherein the conjugate composition comprises, in reacted form, the silicon dioxide nanoparticles surface modified with the linker and the azole such that:
the silicon of the linker forms a covalent bond to at least one of the oxygen atoms of the silicon dioxide of the silicon dioxide nanoparticles, and
the azole is covalently bonded with a carbon atom of the oxirane of the linker via ring-opening of the oxirane with the azole.

2. The method of claim 1 , wherein the linker comprises (3-glycidyloxypropyl)-trimethoxysilane and/or (3-glycidyloxypropyl)-triethoxysilane.

3. The method of claim 1 , wherein the reacting occurs in an alcohol at a temperature in a range of from 60 to 120° C., for a time period in a range of from 2 to 6 hours.

4. The method of claim 1 , wherein, prior to the heating, a pH of the mixture is made basic.

5. The method of claim 1 , wherein the silicon dioxide nanoparticles used in the mixing comprise at least 85 wt. % silica, based on the total nanoparticle weight.

6. The method of claim 1 , wherein the azole is covalently bonded with a carbon atom of the oxirane of the linker via ring-opening of the oxirane with the azole as a substituted hydroxymethine-methylene-azole unit.

7. The method of claim 1 , wherein the azole is 1,2,4-triazole, 3-amino-1,2,4-triazole, 5-aminotetrazole, 1H-benzotriazole, or imidazole.

8. The method of claim 1 , wherein the silicon dioxide nanoparticles used in the mixing comprise at least 97.5 wt. % silica, relative to the total nanoparticle weight.

9. The method of claim 1 , wherein the linker of Formula (1) has Formula (1a):
(C 1-3 O—) 3 —Si—C 2-5 —O—C 1-3 -oxirane  (1a).

Assignees

• Univ Imam Abdulrahman Bin Faisal

Inventors

• Asiri Sarah Mousa
• Khan Firdos Alam
• Bozkurt Ayhan

Classifications

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · 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 Primary

  Antineoplastic agents · CPC title

• A61K47/6935

  the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol · CPC title