# US 11,110,183 B2 · Method of delivering genes and drugs to a posterior segment of an eye

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- Number: US 11,110,183 B2
- Document ID: US11110183B2
- Status: Granted
- Kind: B2
- Application number: 16/531,734
- Filed: 2019-08-05
- Published: 2020-02-27
- Granted: 2021-09-07
- Earliest claimed: 2018-08-03
- Assignees: University of South Florida; The United States Government as represented by the Department of Veterans Affairs
- Applicants: Shyam S. Mohapatra; Subhra Mohapatra; Eleni Markousta
- Inventors: Shyam S. Mohapatra; Subhra Mohapatra; Eleni Markousta
- Web page: https://patentgrep.com/patent/US11110183B2

## 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 9/0048: {Eye, e.g. artificial tears}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 47/549: {Sugars, nucleosides, nucleotides or nucleic acids}
- A61K 47/595: {Polyamides, e.g. nylon (polyamino acids A61K47/62)}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)}
- A61P 27/02: Ophthalmic agents
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 2310/122: Hairpin
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/351: Conjugate
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2320/31: Combination therapy
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A multifunctional dendrimer nanoparticle and method of treating diseases of the posterior segment of the eye is presented. The functionalized polyamidoamine (PAMAM) dendrimer effectively delivers drugs and/or genes to the posterior eye, thereby providing for the effective, non-invasive, and topical treatment of diseased in the posterior eye. The multifunctional dendrimer nanoparticle has shRNA-encoding DNA and small molecule drug encapsulated cyclodextrin complexed to the outer surface of the dendrimer for delivery to the posterior segment of the eye.

## Claims

### Claim 1

A drug delivery system for delivering a drug to a posterior segment of an eye of a patient comprising:
a multifunctional dendrimer-based nanoparticle (MDN) comprising
at least one modified polyamidoamine (PAMAM) dendrimer nanoparticle modified by using molecular extrusion to remove large particles and aggregates to obtain a size of about 10 nm;
at least one short hairpin RNA (shRNA)-encoding DNA molecule complexed to an outer surface of the at least one modified PAMAM dendrimer nanoparticle;
at least one natural cyclodextrin encapsulating pioglitazone on the outer surface of the at least one modified PAMAM dendrimer nanoparticle; and
a targeting agent targeting a CD44 receptor conjugated to the outer surface of the at least one modified PAMAM dendrimer nanoparticle wherein the targeting agent is selected from the group consisting of hyaluronic acid, cholera toxin B domain, arginylglycylaspartic acid (RGD) peptide, and Tat peptide; and
a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The drug delivery system of claim 1, wherein the natural cyclodextrin is β- or γ-clclodextrin.

### Claim 3 (depends on 1)

The drug delivery system of claim 1, further comprising polyethylene glycol (PEG) conjugated to the outer surface of the at least one PAMAM dendrimer nanoparticle.

### Claim 4 (depends on 1)

The drug delivery system of claim 1, wherein the at least one shRNA-encoding DNA molecule is a dual expressing short hairpin RNA (shRNA) recombinant plasmid.

### Claim 5 (depends on 1)

The drug delivery system of claim 1, wherein the PAMAM is G4 PAMAM.

### Claim 6 (depends on 1)

The drug delivery system of claim 1, wherein the ratio of dendrimer to DNA is 1:5.