Nanoparticles for treatment of choroidal neovascularization and other indications

Patent metadata

Field	Value
Publication number	US-11559586-B2
Application number	US-201917057630-A
Country	US
Kind code	B2
Filing date	May 21, 2019
Priority date	May 22, 2018
Publication date	Jan 24, 2023
Grant date	Jan 24, 2023

Abstract

The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides. Other aspects are generally directed to methods of making or using such particles, kits involving such particles, or the like.

First claim

What is claimed is:

1. A composition, comprising:
a polymeric particle comprising a core and a shell; and
an activatable agent present within the shell, the activatable agent comprising a photocleavable entity comprising 7-(diethylamino)coumarin-4-yl]methyl carboxyl (DEACM) and a targeting moiety comprising CGGFRKKRRQRRR (SEQ ID NO. 1), wherein the targeting moiety is inhibited from recognizing a target,
wherein a polymer of the polymeric particle comprises a block copolymer of polylactic acid-poly(ethylene glycol) (PLA-PEG).

2. The composition of claim 1 , wherein the targeting moiety is inhibited from recognizing a target by the photocleavable entity.

3. The composition of claim 1 , wherein the targeting moiety is not present on an outer surface of the particle.

4. The composition of claim 1 , wherein the targeting moiety is present at a concentration of at least 20% by mass relative to the volume of the polymeric particle.

5. The composition of claim 1 , wherein the activatable agent is covalently bound to at least some of the PLA-PEG block copolymer.

6. The composition of claim 5 , wherein the activatable agent is covalently bound to at least some PLA-PEG block copolymer and comprises 20% to 40% by mass of the PLA-PEG block copolymer within the polymeric particle.

7. The composition of claim 1 , wherein the activatable agent is covalently bound to PLA via maleimide-thiol coupling.

8. The composition of claim 1 , wherein the polymeric particle is a nanoparticle.

9. The composition of claim 8 , wherein the nanoparticle comprises a drug.

10. The composition of claim 9 , wherein the drug comprise doxorubicin.

11. A method, comprising:
administering, to a subject, a plurality of polymeric nanoparticles such that at least some of the nanoparticles enter systemic circulation within the subject, the polymeric nanoparticles comprising a core, a shell, and an activatable agent present within the shell, the activatable agent comprising a cell-penetrating peptide comprising CGGFRKKRRQRRR (SEQ ID NO. 1) and a photocleavable entity comprising DEACM, wherein the cell-penetrating peptide is inhibited from recognizing a target; and
applying light to an eye of the subject, wherein the light cleaves the photocleavable entity to separate at least a portion of the photocleavable entity from the activatable agent, wherein upon separation, the cell-penetrating peptide is able to recognize a target on the surface of a cell,
wherein a polymer of the polymeric particle comprises PLA-PEG block copolymer.

12. A method, comprising:
providing a polymeric nanoparticle comprising a core, a shell, and an activatable agent present within the shell, the activatable agent comprising a cell-penetrating peptide comprising CGGFRKKRRQRRR (SEQ ID NO. 1) and a photocleavable entity comprising DEACM, the cell-penetrating peptide being inhibited from recognizing a target; and
applying light to the photocleavable entity to cleave the photocleavable entity to separate at least a portion of the photocleavable entity from the activatable agent, wherein upon separation, the cell-penetrating peptide is able to recognize a target on the surface of a cell,
wherein a polymer of the polymeric particle comprises PLA-PEG block copolymer.

Assignees

• Childrens Medical Center

Inventors

• Kohane Daniel S
• Wang Yanfei

Classifications

• A61K41/0042

  Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K47/68

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title

• A61K47/6937 Primary

  the polymer being PLGA, PLA or polyglycolic acid · CPC title

• A61P27/02 Primary

  Ophthalmic agents · CPC title