# US 9,433,581 B2 · Poly(vinyl benzoate) nanoparticles for molecular delivery

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,433,581 B2
- Document ID: US9433581B2
- Status: Granted
- Kind: B2
- Application number: 13/897,868
- Filed: 2013-05-20
- Published: 2013-09-19
- Granted: 2016-09-06
- Earliest claimed: 2010-11-18
- Assignees: University of South Florida
- Applicants: Edward Turos; Raphael Labruere; Ryan Scott Cormier; Renaud Sicard
- Inventors: Edward Turos; Raphael Labruere; Ryan Scott Cormier; Renaud Sicard
- Web page: https://patentgrep.com/patent/US9433581B2

## CPC

- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/10: Dispersions; Emulsions
- A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/6933: {the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol}
- A61K 49/0039: {Coumarin dyes}
- A61K 49/0043: {Fluorescein, used in vivo}
- A61K 49/0093: {Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle}
- 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)

## Abstract

The present invention comprises poly(vinyl benzoate) nanoparticle suspensions as molecular carriers. These nanoparticles can be formed by nanoprecipitation of poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring about 200-250 nm in diameter which are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC50>1000 μg/mL) and primary bovine primary aortic endothelial cells (IC50>500 μg/mL), and exert non-observable bactericidal activity against a selection of representative test microbes (MIC>250 μg/mL). Poly(vinyl benzoate) nanoparticles are suitable carriers for molecular delivery of lipophilic small molecules such as drugs pharmaceutical and imaging agents.

## Claims

### Claim 1

A composition of nanoparticles comprising:
at least one biodegradable nanoparticle formed from poly(vinyl benzoate) and a block copolymer based on ethylene oxide and propylene oxide wherein the at least one nanoparticle is capable of entrapping lipophilic substrates;
a pharmaceutically acceptable carrier; and
a lipophilic molecules.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the surfactant prevents opsonization.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the at least one nanoparticle has a mean particle size of between about 50 nm and about 350 nm.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the at least one nanoparticle has a mean particle size of between about 200 nm and about 250 nm.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the size of the lipophilic molecule is up to about 5% by weight.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the lipophilic molecule is an antibacterial agent.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the lipophilic molecule is a drug.

### Claim 8

A method of generating a small molecular drug carrier comprising:
nanoprecipitation of a polymer, further comprising
adding at least one surfactant to water, where the at least one surfactant is a block copolymer based on ethylene oxide and propylene oxide;
dissolving or diluting poly(vinyl benzoate) in acetone;
dissolving a predetermined quantity of lipid-soluble molecule in the acetone;
adding the poly(vinyl benzoate)-acetone solution to the water to form a mixture of a block copolymer based on ethylene oxide and propylene oxide and poly(vinyl benzoate);
stirring the mixture of a block copolymer based on ethylene oxide and propylene oxide and poly(vinyl benzoate); and
evaporating the acetone from the mixture of a block copolymer based on ethylene oxide and propylene oxide and poly(vinyl benzoate) to leave a suspension of polyvinyl benzoate nanoparticles.

### Claim 9 (depends on 8)

The method of claim 8, wherein the poly(vinyl benzoate) is added at about 0.5% (w/v) to the acetone.

### Claim 10 (depends on 8)

The method of claim 8, wherein the a block copolymer based on ethylene oxide and propylene oxide is added at about 0.5% w/v.

### Claim 11 (depends on 8)

The method of claim 8, wherein the acetone is evaporated overnight at room temperature.

### Claim 12 (depends on 8)

The method of claim 8, further comprising washing the polyvinyl benzoate nanoparticles, further comprising:
centrifuging the suspension of polyvinyl benzoate nanoparticles at 10,000 rpm for 10 minutes;
resuspending the pellet formed from the centrifugation in distilled water; and
sonicating the pellet for 1 minute to disperse any aggregates.

### Claim 13 (depends on 8)

The method of claim 8, further comprising:
freezing the polyvinyl benzoate nanoparticles at −70° C.; and
lyophilizing the polyvinyl benzoate nanoparticles for 24 hours.