Lipid bilayer coated mesoporous silica nanoparticles with a high loading capacity for one or more anticancer agents

Patent metadata

Field	Value
Publication number	US-10828255-B2
Application number	US-201414772740-A
Country	US
Kind code	B2
Filing date	Mar 5, 2014
Priority date	Mar 5, 2013
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

A submicron structure comprising a silica body defining a plurality of pores that are suitable to receive molecules therein, and having a surface, and a phospholipid bilayer coating the surface, wherein said submicron structure has a maximum dimension of less than one micron, and wherein the phospholipid bilayer stably seals the plurality of pores; and wherein the submicron structure is a member of a monodisperse population of submicron structures.

First claim

We claim:

1. A method of treating a cancer in a subject, said method comprising:
administering to said subject an effective amount of a composition comprising a plurality of drug delivery carriers, wherein said drug delivery carriers each comprise:
a silica body having a plurality of pores suitable to receive a therapeutic agent therein, and having a surface;
an intact lipid bilayer coating the surface and encapsulating said silica body and stably sealing said plurality of pores, wherein said encapsulating is performed without lipid phase exchange and without contacting a preformed liposome with the silica body;
a first therapeutic agent within the pores of said silica body where said first therapeutic agent comprises gemcitabine; and
a second therapeutic agent disposed in said lipid bilayer where said second therapeutic agent comprises paclitaxel;

wherein said drug delivery carriers provide a predetermined dose and ratio of first therapeutic agent to second therapeutic agent, said plurality of drug delivery carriers form a monodisperse population of drug delivery carriers; and
wherein said drug delivery carriers have a maximum dimension that ranges from 20 nm to 300 nm.

2. The method of claim 1 , wherein said first therapeutic agent and said second therapeutic agent act synergistically.

3. The method of claim 1 , wherein the drug delivery carriers include about 20% w/w or greater of gemcitabine molecules within the pores of said silica body.

4. The method of claim 1 , wherein the drug delivery carriers include about 30% w/w or greater of gemcitabine molecules within the pores of said silica body.

5. The method of claim 1 , wherein the drug delivery carriers include about 40% w/w or greater of gemcitabine molecules within the pores of said silica body.

6. The method of claim 1 , wherein said drug delivery carriers are administered to a subject systemically.

7. The method of claim 1 , wherein said cancer comprises a cancer of a stroma.

8. The method of claim 7 , wherein said cancer is selected from the group consisting of pancreatic ductal adenocarcinoma (PDAC), prostate cancer, and glioblastoma.

9. The method of claim 8 , wherein said cancer is PDAC.

10. The method of claim 1 , wherein said administration is intravenous or intraarterial administration.

11. The method of claim 1 , wherein said monodisperse population show a deviation in average diameter of 10% or less.

12. The method of claim 1 , wherein said lipid bilayer is formed from a lipid film containing said second therapeutic agent.

13. The method of claim 1 , wherein said drug delivery carriers retain said first therapeutic agent within said silica body without substantial loss for at least 1 week prior to administration to a subject.

14. The method of claim 1 , wherein said drug delivery carriers retain said first therapeutic agent within said silica body with 10% or less loss for at least 1 week prior to administration to a subject.

15. The method of claim 1 , wherein said composition comprises a stable colloidal suspension.

16. The method of claim 1 , wherein said drug delivery carriers have a maximum dimension that ranges from 50 nm to 200 nm.

Assignees

• Univ California

Inventors

• Nel Andre E
• Zink Jeffrey I
• Meng Huan

Classifications

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• A61K9/5115

  Inorganic compounds · CPC title

• A61K45/06

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