# US 12,551,527 B2 · Drug delivery systems for treatment of infections

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- Number: US 12,551,527 B2
- Document ID: US12551527B2
- Status: Granted
- Kind: B2
- Application number: 16/958,647
- Filed: 2018-12-28
- Published: 2020-11-26
- Granted: 2026-02-17
- Earliest claimed: 2017-12-29
- Assignees: Wayne State University
- Applicants: Wayne State University
- Inventors: Arun K. Iyer; Samaresh Sau; Michael Rybak; Ketki Bhise; Razie Kebriaei
- Web page: https://patentgrep.com/patent/US12551527B2

## CPC

- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 31/546: containing further heterocyclic rings, e.g. cephalothin
- A61K 47/545: {Heterocyclic compounds (A61K47/558 takes precedence)}
- A61K 47/551: {one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid}
- A61K 47/6911: {the form being a liposome}
- A61L 15/44: Medicaments
- A61L 15/46: Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 31/04: Antibacterial agents
- A61L 2300/406: Antibiotics
- A61L 2300/626: Liposomes, micelles, vesicles
- A61L 2300/64: Animal cells
- A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Lipid-based drug delivery vehicles (including liposomal nanoparticles) are described which include antibiotic(s) for the treatment of infections, such as Methicillin-Resistant Staphylococcus (S.) aureus (MRSA) infections and Methicillin-Susceptible S. aureus (MSSA) infections. These drug delivery vehicles have high drug-loading, do not accumulate in the liver, and can optionally include one or more targeting ligands.

## Claims

### Claim 1

A method of treating Staphylococcus (S.) aureus infection in a subject in need thereof, comprising:
administering a therapeutically effective amount of a drug delivery system comprising vancomycin and cefazolin to the subject wherein the drug delivery system comprises a liposomal nanoparticle comprising:
a lipid component comprising:
a 1:0.5:0.07 ratio of hydro soy phosphatidylcholine (HSPC) to cholesterol to methoxyl polyethylene glycol (PEG)-ylated distearoyl-phosphatidyl-ethanolamine (DSPE-mPEG), or
a 1:0.05:0.007:0.007 ratio of HSPC to cholesterol to DSPE-mPEG to DSPE-PEG-Folate, or
a 1:0.5:0.07 ratio of N-(1-(2,3-dioleoyloxy) propyl)-N,N,N-trimethylammonium chloride (DOTAP) to cholesterol to DSPE-mPEG; and
wherein the liposomal nanoparticle encapsulates:
at least 10% vancomycin; and
cefazolin, and
wherein the nanoparticle comprises a 1:1 drug:lipid ratio,
thereby treating the S. aureus infection in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the liposomal nanoparticle was made using a modified water in oil (reverse phase) evaporation method described herein.

### Claim 3 (depends on 1)

The method of claim 1, wherein the S. aureus infection is a Methicillin-Resistant Staphylococcus aureus (MRSA) infection or a Methicillin-Susceptible S. aureus (MSSA) infection.

### Claim 4 (depends on 1)

The method of claim 1, wherein the drug delivery system comprises a targeting ligand, wherein the targeting ligand is selected from a leucocyte targeting ligand, a fibroblast targeting ligand, a neutrophil targeting ligand, a lymphocyte targeting ligand, a targeting ligand specific to a bacterial cell, or a targeting ligand specific to the cell of a host cell associated with a bacterial cell.

### Claim 5 (depends on 4)

The method of claim 4, wherein the targeting ligand is a folate receptor beta (FRβ), a toll-like receptor (TLR), a hyaluronan receptor, a T cell receptor (TCR) of immune cells, a protein A receptor on the surface of S. aureus, or an extracellular protein expressed by leukocytes.

### Claim 6 (depends on 4)

The method of claim 4, wherein the drug delivery system comprises one or more of folic acid, methotrexate, aminopterin, an antibody, peptides for targeting folate receptor (FR), lipopeptides, lipoprotein, small oligonucleotide sequences for targeting toll-like receptor (TLR), hyaluronic acid (HA) for targeting cluster of differentiation (CD)44, linagliptin, and/or other xanthine scaffold for targeting fibroblast activation protein (FAP) of wound fibroblast cells.

### Claim 7 (depends on 4)

The method of claim 4, wherein the leucocyte targeting ligand is folic acid or another folate receptor ligand.

### Claim 8 (depends on 1)

The method of claim 1, wherein the drug delivery system comprises a carbonic anhydrase (CA) targeting ligand.

### Claim 9 (depends on 8)

The method of claim 8, wherein the CA targeting ligand comprises imidazole, sulfoimidazole derivative, acetazolamide; methazolamide; ethoxzolamide; dichorophenamide; dorzolamide; brinzolamide; benzolamide; topiramate; zonisamide; sulpiride; indisulam; celecoxib; valdecoxib; antibody, or a peptide.

### Claim 10 (depends on 8)

The method of claim 8, wherein the CA targeting ligand is acetazolamide.

### Claim 11 (depends on 4)

The method of claim 4, wherein the targeting ligand, the vancomycin, and/or the cefazolin is chemically conjugated with lipid molecule(s) of the liposomes.

### Claim 12 (depends on 1)

The method of claim 1, wherein the nanoparticle comprises at least 30% vancomycin.

### Claim 13 (depends on 1)

The method of claim 1, wherein the nanoparticle is within a population of nanoparticles having a mean diameter of 192.9 nm, or having a mean diameter of 176.5 nm.

### Claim 14 (depends on 5)

The method of claim 5, wherein the hyaluronan receptor is CD44.