# US 2014/0193508 A1 · Surface binding of nanoparticle based drug delivery to tissue

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- Number: US 2014/0193508 A1
- Document ID: US20140193508A1
- Status: Published application
- Kind: A1
- Application number: 14/147,863
- Filed: 2014-01-06
- Published: 2014-07-10
- Earliest claimed: 2013-01-04
- Assignees: Massachusetts Institute of Technology
- Applicants: Massachusetts Institute of Technology
- Inventors: Ambika Goel Bajpayee; Alan Grodzinsky; Cliff Richard Wong; Moungi G. Bawendi
- Web page: https://patentgrep.com/patent/US20140193508A1

## CPC

- A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)}
- 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 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 38/18: Growth factors; Growth regulators
- 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 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 47/645: {Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT}
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 19/10: for osteoporosis
- A61P 21/06: Anabolic agents (androgens A61P5/26)
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

## Abstract

Microparticles and nanoparticles and compositions thereof are provided. The microparticles and nanoparticles and compositions may be used for the treatment of musculoskeletal disease, such as osteoarthritis and injury.

## Claims

### Claim 1

A method for delivering an active agent to a connective tissue in a subject, comprising:
administering to a subject, a microparticle having an average particle size of greater than 10 nm, wherein the microparticle is functionalized with a connective tissue binding compound and includes a first active agent, wherein the active agent is delivered to the connective tissue as it is released from the microparticle, wherein the active agent is a therapeutic agent for the treatment of musculoskeletal disease or injury.

### Claim at position 2

2-3. (canceled)

### Claim 4 (depends on 1)

The method of claim 1, wherein the connective tissue binding compound is avidin.

### Claim at position 4

5-6. (canceled)

### Claim 7 (depends on 1)

The method of claim 1, further comprising a nanoparticle having an average particle size of 10 nm or less, wherein the nanoparticle includes a second active agent.

### Claim at position 6

8-23. (canceled)

### Claim 24

A composition comprising:
a microparticle having an average particle size of greater than 10 nm, wherein the microparticle is functionalized with a connective tissue binding compound and includes a first active agent, and a nanoparticle having an average particle size of 10 nm or less, wherein the nanoparticle includes a second active agent.

### Claim 25 (depends on 24)

The composition of claim 24, wherein the microparticle comprises a polymer.

### Claim 26 (depends on 24)

The composition of claim 24, wherein the microparticle comprises a peptide.

### Claim 27 (depends on 26)

The composition of claim 26, wherein the peptide is 5 amino acids or more from the amino acid sequence of SEQ ID NO 1.

### Claim 28 (depends on 26)

The composition of claim 26, wherein the peptide is 15 amino acids or more from the amino acid sequence of SEQ ID NO 1.

### Claim at position 12

29-54. (canceled)

### Claim 55

A method for delivering an active agent to a connective tissue in a subject, comprising:
administering to a subject, nanoparticle having an average particle size of 10 nm or less, wherein the nanoparticle comprises a polymer having a net positive charge of greater than 6, wherein the nanoparticle is functionalized with an active agent.

### Claim 56 (depends on 55)

The method of claim 55, wherein the polymer has a molecular weight of 60-90 kd.

### Claim 57 (depends on 55)

The method of claim 55, wherein the polymer has a molecular weight of 60-80 kd.

### Claim 58 (depends on 55)

The method of claim 55, wherein the polymer has a molecular weight of 60-70 kd.

### Claim 59 (depends on 55)

The method of claim 55, wherein the polymer is a peptide.

### Claim 60 (depends on 59)

The method of claim 59, wherein the peptide is 5 amino acids or more from the amino acid sequence of SEQ ID NO 1.

### Claim 61 (depends on 59)

The method of claim 59, wherein the peptide is 15 amino acids or more from the amino acid sequence of SEQ ID NO 1.

### Claim 62 (depends on 55)

The method of claim 55, wherein the nanoparticle comprises a polymer having a net positive charge of 6-20.

### Claim 63 (depends on 62)

The method of claim 62, wherein the nanoparticle comprises a polymer having a net positive charge of 7-14.

### Claim 64

(canceled)

### Claim 65 (depends on 55)

The method of claim 55, wherein the active agent is selected from the group consisting of dexamethasone, Disease Modifying Osteoarthritis Drug (DMOAD), pro-anabolic growth factors including IGF (Insulin like Growth Factors), IGF-1, FGF-15, and BMP7, and anti-catabolic agents including glucocorticoid class of steroid drug such as Triamcinolone, blockers of inflammatory cytokines, inhibitors of TNF, IL-1, Aggrecanases and Matrix Metalloproteinases.

### Claim 66

A composition comprising:
a nanoparticle having an average particle size of 10 nm or less, wherein the nanoparticle includes an active agent, wherein the active agent is a therapeutic agent for the treatment of disease condition of a bone or connective tissue and wherein the nanoparticle comprises a polymer having a net positive charge of greater than 6.

### Claim 67 (depends on 66)

The composition of claim 66, wherein the polymer has a molecular weight of less than 90 kd.

### Claim 68 (depends on 66)

The composition of claim 66, wherein the polymer has a molecular weight of 10 kd-90 kd.

### Claim 69 (depends on 66)

The composition of claim 66 wherein the therapeutic agent is IGF.

### Claim 70 (depends on 66)

The composition of claim 66, wherein the polymer has a molecular weight of 60-90 kd.

### Claim 71 (depends on 66)

The method of claim 66, wherein the polymer has a molecular weight of 60-80 kd.

### Claim 72 (depends on 66)

The method of claim 66, wherein the polymer has a molecular weight of 60-70 kd.

### Claim 73 (depends on 66)

The composition of claim 66, wherein the polymer is a peptide.

### Claim 74 (depends on 73)

The composition of claim 73, wherein the peptide is 5 amino acids or more from the amino acid sequence of SEQ ID NO 1.

### Claim 75 (depends on 73)

The composition of claim 73, wherein the peptide is 15 amino acids or more from the amino acid sequence of SEQ ID NO 1.

### Claim 76 (depends on 66)

The composition of claim 66, wherein the nanoparticle comprises a polymer having a net positive charge of 6-20.

### Claim 77 (depends on 76)

The composition of claim 76, wherein the nanoparticle comprises a polymer having a net positive charge of 7-14.

### Claim 78 (depends on 66)

The composition of claim 66, wherein the peptide is selected from the group consisting of avidin, albumin, gelatin, lysozyme and amphilic triblock peptides.

### Claim 79

A composition comprising:
a nanoparticle of avidin or a fragment thereof and a therapeutic agent selected from the group consisting of a Disease Modifying Osteoarthritis Drug (DMOAD), a pro-anabolic growth factors and an anti-catabolic agent.

### Claim at position 38

80-86. (canceled)