Means and methods for ocular drug delivery

Patent metadata

Field	Value
Publication number	US-2016346203-A1
Application number	US-201415022219-A
Country	US
Kind code	A1
Filing date	Sep 17, 2014
Priority date	Sep 17, 2013
Publication date	Dec 1, 2016
Grant date	—

Abstract

The invention relates to compositions and methods that utilize polymeric nanoparticles to deliver a therapeutic compound to ocular cells or ocular tissue. Provided is a drug-loaded micelle comprising self-assembled amphiphilic biopolymers, such as hydrophobically modified nucleic acids or polypeptides, for use as ophthalmic drug delivery system. Also provided are ophthalmic compositions and methods for preventing or treating an ophthalmic disease.

First claim

1 . A drug-loaded micelle comprising self-assembled amphiphilic biopolymers for use in a method for preventing or treating an ophthalmic disease or disorder, wherein said amphiphilic biopolymer is a nucleic acid molecule comprising at the 3′ or 5′ end a stretch of at least 2 contiguous hydrophobically-modified nucleotides which are modified at the nucleobase, ribose or phosphate group with a hydrophobic moiety.

2 . The micelle according to claim 1 , wherein said amphiphilic biopolymer is a nucleic acid molecule consisting of 10 to 20 nucleotides, wherein the hydrophobic moiety at the 3′ or 5′end is formed by 2 to 6 contiguous hydrophobically-modified nucleotides.

3 . The micelle according to claim 1 , wherein the hydrophobic moiety is a hydrocarbon chain, preferably comprising at least 10 C-atoms.

4 . The micelle according to claim 3 , wherein the hydrocarbon chain is a straight C10-C20 alkyl chain.

5 . The micelle according to claim 1 , wherein the contiguous hydrophobically-modified nucleotides have the same hydrophobic groups.

6 . The micelle according to claim 1 , wherein the contiguous hydrophobically-modified nucleotides have distinct hydrophobic groups.

7 . The micelle according to claim 1 , comprising a hydrophobic drug enclosed in the hydrophobic core of the micelle.

8 . The micelle according to claim 1 , wherein the hydrophilic moiety of at least one amphiphile is provided with a drug.

9 . The micelle according to claim 8 , wherein the hydrophilic moiety is a first nucleic acid and wherein the drug is attached to the hydrophilic moiety via a hybridized second nucleic acid provided with a drug.

10 . The micelle according to claim 9 , wherein the drug is covalently bound to said hybridized second nucleic acid.

11 . The micelle according to claim 9 , wherein the drug is bound to said hybridized second nucleic acid via an aptameric interaction.

12 . A drug-loaded micelle comprising self-assembled amphiphilic first nucleic acid molecules provided at the 3′ or 5′ end with a hydrophobic moiety and wherein at least one drug is attached to the first nucleic acid molecule via a hybridized second nucleic acid that is provided with a drug.

13 . The micelle according to claim 1 , wherein the drug is an ophthalmic drug selected from the group consisting of anti-glaucoma agents, anti-angiogenesis agents, anti-infective agents, non-steroidal and steroidal anti-inflammatory agents, growth factors, immunosuppressant agents, anti-allergic agents, and any combination or pro-drug form thereof.

14 . The micelle according to claim 13 , wherein the drug is an aminoglycoside antibiotic.

15 . The micelle according to claim 14 , wherein the antibiotic is neomycin, kanamycin or a derivative thereof.

16 . The micelle according to claim 13 , wherein the drug is a prostaglandin.

17 . The micelle according to claim 16 , wherein the prostaglandin is selected from the group consisting of latanoprost, bimatoprost, tafluprost, unoprostone and travoprost.

18 . The micelle according to claim 13 , wherein the drug is an adrenergic agonists, preferably apraclonidine or brimonidine.

19 . An ophthalmic composition comprising a drug-loaded micelle of claim 1 .

20 . The ophthalmic composition according to claim 19 , in the form of an aqueous solution, suspension or gel.

21 . A method for preventing or treating a disease and/or disorder in the ophthalmic field, comprising administering to the eye of a subject in need thereof an effective amount of a drug-loaded micelle according to claim 1 .

22 . The method according to claim 21 , wherein the disease and/or disorder is selected from the group consisting of glaucoma, infections, inflammations, allergies, dry eye disease, AMD, Diabetic retinopathy, diabetic macular edema, retinal vein occlusion, uveitis, post operative macular edema and herpetic eye disease.

23 . The method according to claim 22 , wherein the micelle is loaded with an anti-glaucoma drug.

24 . An ophthalmic composition comprising a drug-loaded micelle of claim 12 .

25 . A method for preventing or treating a disease and/or disorder in the ophthalmic field, comprising administering to the eye of a subject in need thereof an effective amount of a drug-loaded micelle according to claim 12 .

Assignees

• Univ Groningen
• Eberhard- Karls- Universität Tübingen Medizinische Fakultät

Inventors

• Herrmann Andreas
• De Vries Jan Willem
• Spitzer Martin Stephan
• Schinchels Sven Oliver

Classifications

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K31/557

  Eicosanoids, e.g. leukotrienes {or prostaglandins} · CPC title

• A61K47/6907

  the form being a microemulsion, nanoemulsion or micelle · CPC title

• A61K9/0048 Primary

  Eye, e.g. artificial tears · CPC title