# US 9,517,246 B2 · Chitosan derivatives for inactivation of endotoxins and surface protection of nanoparticles

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- Number: US 9,517,246 B2
- Document ID: US9517246B2
- Status: Granted
- Kind: B2
- Application number: 15/212,771
- Filed: 2016-07-18
- Published: 2016-11-10
- Granted: 2016-12-13
- Earliest claimed: 2011-09-27
- Assignees: Purdue Research Foundation
- Applicants: Purdue Research Foundation
- Inventors: Yoon Yeo; Gaurav Bajaj; Peisheng Xu; Karen Liu; Eun Jung Cho
- Web page: https://patentgrep.com/patent/US9517246B2

## CPC

- A61K 31/722: Chitin, chitosan
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- A61P 35/00: Antineoplastic agents
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C08B 37/003: {Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof}
- C08J 3/16: by coagulating dispersions {(C08J3/122 takes precedence)}
- C08L 5/08: Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
- C08L 79/02: Polyamines
- C08L 101/005: {Dendritic macromolecules}
- C08J 2300/202: Dendritic macromolecules, e.g. dendrimers or hyperbranched polymers
- C08J 2405/08: Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
- C08L 2205/18: Spheres
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 2)

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.

### Claim 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.

### Claim 6 (depends on 5)

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

### Claim 7 (depends on 5)

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.

### Claim 8 (depends on 6)

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.