# US 10,369,230 B2 · Sustained release of a therapeutic agent from PLA-PEG-PLA nanoparticles for cancer therapy

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- Number: US 10,369,230 B2
- Document ID: US10369230B2
- Status: Granted
- Kind: B2
- Application number: 15/480,817
- Filed: 2017-04-06
- Published: 2018-10-11
- Granted: 2019-08-06
- Earliest claimed: 2017-04-06
- Assignees: National Guard Health Affairs; King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center
- Applicants: National Guard Health Affairs; King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center
- Inventors: Salam Massadeh; Manal Alaamery
- Web page: https://patentgrep.com/patent/US10369230B2

## CPC

- A61K 47/6935: {the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol}
- A61K 31/4196: 1,2,4-Triazoles
- A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K 47/6937: {the polymer being PLGA, PLA or polyglycolic acid}
- C07K 16/32: against translation products of oncogenes
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

A nanoparticle that has a membrane including a polylactide-block-poly(ethylene glycol)-block-polylactide (PLA-PEG-PLA) and a polyvinyl alcohol, a bovine serum albumin contacting the membrane on the outside of the nanoparticle, a targeting group attached to the outside of the nanoparticle, and a breast cancer therapeutic agent that is encapsulated by the membrane. A nanoparticle that consists of a membrane including a polylactide-block-poly(ethylene glycol)-block-polylactide (PLA-PEG-PLA) and a polyvinyl alcohol, a bovine serum albumin contacting the membrane on the outside of the nanoparticle, breast cancer therapeutic agent that is encapsulated by the membrane, and an anti-Her2 antibody attached to the outer surface of the nanoparticle. A range of a number average molecular weight of the PEG block is 800 Da to 3 kDa and a range of a number average molecular weight of each of the PLA blocks is from 1 kDa to 5 kDa.

## Claims

### Claim 1

A nanoparticle having an interior space and a membrane surrounding the interior space,
wherein the interior space contains letrozole that is encapsulated by the membrane, and the membrane comprises;
a polylactide-block-poly(ethylene glycol)-block-polylactide block (PLA-PEG-PLA) copolymer wherein a number average molecular weight range of the PEG block is 800 Da to 3 kDa and a number average molecular weight range of each of the PLA block is from 1 kDa to 5 kDa,
a polyvinyl alcohol polymer,
bovine serum albumin in contact with the outer surface of the membrane, and
anti-Her2 antibody attached to the outer surface of the membrane.

### Claim 2 (depends on 1)

The nanoparticle of claim 1, wherein said nanoparticle provides sustained release of letrozole over a period of 72 hours.

### Claim 3 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle comprises 60 to 95 weight percent of the polylactide-block-poly(ethylene glycol)-block-polylactide block (PLA-PEG-PLA) copolymer and 0.5 to 5 weight percent of polyvinyl alcohol polymer relative to the total weight of the nanoparticle.

### Claim 4 (depends on 1)

The nanoparticle of claim 1, wherein the bovine serum albumin is 0.5 to 8 weight percent relative to the total weight of the nanoparticle.

### Claim 5 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has a diameter of 300 nm to 370 nm.

### Claim 6 (depends on 1)

The nanoparticle of claim 1, wherein a rate of release of the breast cancer therapeutic agent is a cumulative percent of 25% to 75% in 24 hours to 96 hours.

### Claim 7 (depends on 1)

The nanoparticle of claim 1, wherein the anti-Her2 antibody is bound to the membrane via a biotin-avidin complex.

### Claim 8 (depends on 7)

The nanoparticle of claim 7, wherein the anti-Her2 antibody is sourced from a rabbit.

### Claim 9 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has a diameter of from 310 nm to 350 nm.

### Claim 10 (depends on 1)

The nanoparticle of claim 1, wherein the anti-Her2 antibody is conjugated to the membrane.

### Claim 11 (depends on 1)

The nanoparticle of claim 1, wherein the breast cancer therapeutic agent consists letrozole.

### Claim 12 (depends on 1)

The nanoparticle of claim 1, wherein the breast cancer therapeutic agent is 0.5 to 10 weight percent relative to the total weight of the nanoparticle.

### Claim 13 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has an internal volume of from 1 picoliter to 1 nanoliter.

### Claim 14 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has a zeta potential of −7 mV to −20 mV.

### Claim 15 (depends on 1)

The nanoparticle of claim 1, wherein the membrane further comprises a diblock copolymer.

### Claim 16 (depends on 15)

The nanoparticle of claim 15, wherein a weight percent of the diblock copolymer relative to the total weight of the nanoparticle is 0.01% to 0.1%.

### Claim 17 (depends on 15)

The nanoparticle of claim 15, wherein the diblock copolymer comprises one hydrophobic block polymer and one hydrophilic block polymer.

### Claim 18 (depends on 17)

The nanoparticle of claim 17, wherein the diblock copolymer comprises at least one hydrophobic polymer block selected from the group consisting of polycaprolactone (PCL), polyvalerolactone (PVL), poly(lactide-co-glycolide) (PLGA), polylactic acid (PLA), polybutyrolactone (PBL), polyglycolide, and polypropiolactone (PPL), and at least one hydrophilic polymer block selected from the group consisting of polyethylene glycol (PEG), hyaluronic acid (HA), and poly-γ-glutamic acid (PGA).

### Claim 19 (depends on 17)

The nanoparticle of claim 17, wherein a number average molecular weight range of the hydrophobic block polymer and the hydrophilic block polymer is from 800 Da to 5 kDa.

### Claim 20 (depends on 1)

The nanoparticle of claim 1, wherein the membrane is prepared by a double emulsion method comprising mixing a first emulsion with a second emulsion, wherein the first emulsion and the second emulsion comprise polyvinyl alcohol as an emulsifying agent.