Mesoporous silica nanoparticles with a lipid bilayer coating for cargo delivery

Patent metadata

Field	Value
Publication number	US-10765636-B2
Application number	US-201816164030-A
Country	US
Kind code	B2
Filing date	Oct 18, 2018
Priority date	Jan 8, 2016
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

A nanocarrier including a silica body having a surface and defining a plurality of pores that are suitable to receive molecules therein is described. The nanocarrier also includes a lipid bilayer coating the surface, and a cargo-trapping agent within the phospholipid bilayer. The phospholipid bilayer stably seals the plurality of pores. The cargo-trapping reagent can be selected to interact with a desired cargo, such as a drug.

First claim

What is claimed is:

1. A method of treating cancer, comprising administering to a subject in need thereof an effective amount of a nanoparticle drug carrier, wherein the nanoparticle drug carrier comprises:
a) a silica nanoparticle having a surface and defining a plurality of pores;
b) a lipid bilayer coating the surface;
c) a protonating agent disposed within the plurality of pores where said protonating agent is an ammonium salt, a trimethylammonium salt, a triethylammonium salt, or an ionophore combined with a metal salt; and
d) a drug disposed within the plurality of pores, wherein said drug consists of irinotecan, and wherein the nanoparticle drug carrier has a drug loading capacity of at least about 40% w/w.

2. The method of claim 1 , wherein the nanoparticle drug carrier has less than about 15% leakage of the drug over 20 hours in a biological buffer with pH of 7.4 at 37° C.

3. The method of claim 1 , wherein a plurality of nanoparticle drug carriers has a median diameter of less than one micron.

4. The method of claim 1 , wherein the nanoparticle drug carrier comprises a remote loading agent disposed within the plurality of pores.

5. The method of claim 1 , wherein the protonating agent converts the drug into a hydrophilic derivative that is incapable of back diffusion across the lipid bilayer.

6. The method of claim 1 , wherein the protonating agent comprises at least one anionic group.

7. The method of claim 1 , wherein the protonating agent before reaction with the drug comprises an ammonium salt, a trimethylammonium salt, or a triethylammonium salt.

8. The method of claim 7 , wherein the drug is protonated by the protonating agent and trapped in the plurality of pores as a gel-like precipitate.

9. The method of claim 7 , wherein the ammonium salt is selected from the group consisting of ammonium sulfate, ammonium sucrose octasulfate, ammonium α-cyclodextrin sulfate, ammonium β-cyclodextrin sulfate, ammonium γ-cyclodextrin sulfate, ammonium phosphate, ammonium α-cyclodextrin phosphate, ammonium β-cyclodextrin phosphate, ammonium γ-cyclodextrin phosphate, ammonium citrate, and ammonium acetate.

10. The method of claim 7 , wherein the trimethylammonium salt is selected from the group consisting of trimethylammonium sulfate, trimethylammonium sucrose octasulfate, trimethylammonium α-cyclodextrin sulfate, trimethylammonium β-cyclodextrin sulfate, trimethylammonium γ-cyclodextrin sulfate, trimethylammonium phosphate, trimethylammonium α-cyclodextrin phosphate, trimethylammonium β-cyclodextrin phosphate, trimethylammonium γ-cyclodextrin phosphate, trimethylammonium citrate, and trimethylammonium acetate.

11. The method of claim 7 , wherein the triethylammonium salt is selected from the group consisting of triethylammonium sulfate, triethylammonium sucrose octasulfate, triethylammonium α-Cyclodextrin sulfate, triethylammonium β-Cyclodextrin sulfate, triethylammonium γ-Cyclodextrin sulfate, triethylammonium phosphate, triethylammonium α-Cyclodextrin phosphate, triethylammonium β-Cyclodextrin phosphate, triethylammonium γ-Cyclodextrin phosphate, triethylammonium citrate, and triethylammonium acetate.

12. The method of claim 7 , wherein the protonating agent before reaction with the drug comprises triethylammonium sucrose octasulfate (TEA8SOS).

13. The method of claim 1 , wherein the nanoparticle drug carrier is a primary therapy in a chemotherapeutic regimen.

14. The method of claim 1 , wherein the nanoparticle drug carrier is a component in a multi-drug chemotherapeutic regimen.

15. The method of claim 14 , wherein the multi-drug chemotherapeutic regimen comprises at least two drugs selected from the group consisting of irinotecan (IRIN), oxaliplatin (OX), 5-fluorouracil (5-FU), and leucovorin (LV).

16. The method of claim 1 , wherein the cancer is pancreatic cancer, colorectal cancer, breast cancer, lung cancer, liver cancer, glioma, or melanoma.

17. The method of claim 1 , wherein the cancer is pancreatic ductal adenocarcinoma (PDAC).

Assignees

• Univ California

Inventors

• Nel Andre E
• Meng Huan
• Liu Xiangsheng

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K47/6929

  the form being a nanoparticle, e.g. an immuno-nanoparticle · CPC title

• A61K47/6923

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

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title