Core-shell particle formulation for delivering multiple therapeutic agents

Patent metadata

Field	Value
Publication number	US-9707186-B2
Application number	US-201414585013-A
Country	US
Kind code	B2
Filing date	Dec 29, 2014
Priority date	Feb 21, 2012
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

A core-shell particle formulation for delivering multiple therapeutic agents is disclosed. More particularly, the formulation comprising protein-protein core-shell particle configured to independently release therapeutic agents from the core and the shell. Moreover, the core-shell particle bearing therapeutic agents enable treatment against the diseases such as cancer, inflammatory and auto-immune diseases.

First claim

What is claimed is:

1. A core-shell particle formulation for delivering multiple therapeutic agents comprising:
a protein core comprising protamine loaded with a first therapeutic agent; and
a protein shell encapsulating the core to form a particle formulation, wherein the protein shell comprises cross-linked serum albumin loaded with a second therapeutic agent;
wherein the first therapeutic agent of the core comprise siRNA and the second therapeutic agent of the shell comprise sorafenib;
wherein the particle is configured to independently release the therapeutic agents from the core and the shell; and
wherein the therapeutic agents are configured to be delivered by active targeting by conjugating the core-shell formulation with transferrin.

2. The formulation of claim 1 , wherein the size of the core-shell particle is 1-1000 nm.

3. The formulation of claim 1 , wherein the core or the shell further comprise lactoferrin, fibrinogen, gelatin, mucin, soy protein, apoferritin, ferritin, lectin, gluten, whey protein, prolamines, gliadin, hordein, secalin, zein, or avenin.

4. The formulation of claim 1 , wherein the core or shell is further loaded with small molecule kinase inhibitors, phytochemicals, deoxyribozymes, ribozymes, shRNA, DNA, PNAs, or miRNAs.

5. The formulation of claim 1 , wherein the core or shell is further loaded with demethylation agents, retinoids, antimetabolites, antimicrotubule agents, anti-angiogenesis agents, alkylating agents, biologic response modifiers, antitumor antibiotics, proteasome inhibitors, topoisomerase I inhibitors, hormones, immunomodulators, monoclonal antibodies, aromatase inhibitors, glucocorticosteroids, cytokines, enzymes, anti-androgen molecules, epigenetic modifiers, imatinib, nilotinib, erlotinib, gefitinib, dasatinib, or everolimus.

6. The formulation of claim 1 , wherein the core or the shell or both are embedded with metallic nanoclusters comprising one or more of gold, silver, platinum, copper, or iron.

7. The formulation of claim 1 , wherein the therapeutic agents are configured to be delivered from the shell and core sequentially.

8. The formulation of claim 1 , wherein the therapeutic agents are configured to be delivered from the shell and core simultaneously.

Assignees

• Koyakutty Manzoor
• Nair Shantikumar
• P Retnakumari Archana
• Amrita Vishwa Vidyapeetham

Inventors

• Koyakutty Manzoor
• Nair Shantikumar
• P Retnakumari Archana

Classifications

• A61K9/51

  Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)} · CPC title

• A61K9/5169 Primary

  Proteins, e.g. albumin, gelatin · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K38/40

  Transferrins, e.g. lactoferrins, ovotransferrins · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title