Chitosan derivatives for inactivation of endotoxins and surface protection of nanoparticles

Patent metadata

Field	Value
Publication number	US-9517246-B2
Application number	US-201615212771-A
Country	US
Kind code	B2
Filing date	Jul 18, 2016
Priority date	Sep 27, 2011
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

The present disclosure provides a polymer comprising a derivative of chitosan, wherein the derivative is zwitterionic, as well as methods of using the polymer. In addition, the present disclosure provides a nanoparticle structure comprising a derivative of chitosan and a dendrimer, as well as methods of utilizing the nanoparticle structure.

First claim

What is claimed is:

1. An anti-tumor nanoparticle comprising a non-covalent, electrostatic complex between (1) a conjugate comprising a poly(amidoamine) dendrimer (PAMAM dendrimer) and an anti-tumor agent and (2) a zwitterionic chitosan derivative having an anhydride to amine (An/Am) ratio of 0.3 to 0.7, wherein (A) the zwitterionic chitosan derivative was synthesized by partial amidation of a chitosan with succinic anhydride, (B) the weight ratio of zwitterionic chitosan derivative to PAMAM dendrimer is greater than or equal to 1 but less than or equal to 4, and (C) the size of the anti-tumor nanoparticle is between 250 nm and about 500 nm.

2. The anti-tumor nanoparticle of claim 1 , wherein the PAMAM dendrimer is a generation 5 (G5) dendrimer.

3. A method of treating a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the anti-tumor nanoparticles of claim 1 .

4. A method of treating a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the anti-tumor nanoparticles of claim 2 .

5. An imaging nanoparticle comprising a non-covalent, electrostatic complex between (1) a conjugate comprising a poly(amidoamine) dendrimer (PAMAM dendrimer) and an imaging agent and (2) a zwitterionic chitosan derivative having an anhydride to amine (An/Am) ratio of 0.3 to 0.7, wherein (A) the zwitterionic chitosan derivative was synthesized by partial amidation of a chitosan with succinic anhydride, (B) the weight ratio of zwitterionic chitosan derivative to PAMAM dendrimer is greater than or equal to 1 but less than or equal to 4, and (C) the size of the imaging nanoparticle is between 250 nm and about 500 nm.

6. The imaging nanoparticle of claim 5 , wherein the PAMAM dendrimer is a generation 5 (G5) dendrimer.

7. A method of imaging a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the imaging nanoparticles of claim 5 .

8. A method of imaging a tumor in a mammal, wherein the tumor has a weakly acidic microenvironment of pH 6.5 to 7.2, the method comprising parenterally administering to the mammal an effective amount of the imaging nanoparticles of claim 6 .

Assignees

• Purdue Research Foundation

Inventors

• Yeo Yoon
• Bajaj Gaurav
• Xu Peisheng
• Liu Karen
• Cho Eun Jung

Classifications

• C08L2205/18

  Spheres · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title

• C08J2300/202

  Dendritic macromolecules, e.g. dendrimers or hyperbranched polymers · CPC title

• B82Y5/00

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

• C08J3/16

  by coagulating dispersions {(C08J3/122 takes precedence)} · CPC title