Methods and compositions for targeted delivery of therapeutic agents
Compositions and methods for targeted delivery of therapeutic agents, and particularly for mucosal, oral, nasal, or parenteral delivery of therapeutic agents. The compositions comprise carrier particles containing or encapsulating a therapeutic agent or agents, which have been modified on their surface to contain one or more targeting moieties that enable the enhanced uptake and transport of the therapeutic agent via receptor-mediated processes such as endocytosis or transcytosis.
1. A composition for use in treating or preventing ophthalmic disorders in a mammal by administration to the eye, comprising:
a plurality of poly(lactide) carrier particles comprising a therapeutically effective amount of a therapeutic agent;
a plurality of ocular targeting moieties conjugated to the outer surface of said carrier particles, wherein said ocular targeting moieties are LHRH-receptor targeting moieties, and wherein the therapeutic agent and the ocular targeting moieties are not the same; and
a plurality of transferrin-receptor-targeting moieties conjugated to the outer surface of said carrier particles.
2. The composition of claim 1 , wherein said carrier particles are nanoparticles.
3. The composition of claim 1 , wherein said poly(lactide) is poly(lactide-co-glycolide).
4. The composition of claim 1 , wherein said therapeutic agent is an anti-VEGF agent or anti-angiogenic agent.
5. The composition of claim 1 , wherein said therapeutic agent is a glaucoma therapeutic agent.
6. The composition of claim 1 , wherein said therapeutic agent is a dry eye therapeutic agent.
7. The composition of claim 1 , wherein said therapeutic agent is an antibiotic.
8. The composition of claim 1 , wherein said therapeutic agent is an anti-inflammatory.
9. The composition of claim 1 , wherein said therapeutic agent is a nucleic acid based therapeutic agent selected from the group consisting of oligomers, siRNAs, plasmids, and aptamers.
10. The composition of claim 1 , wherein said carrier particles further comprise a second therapeutic agent.
11. The composition of claim 1 , wherein at least one of said ocular targeting moieties is deslorelin.
12. The composition of claim 1 , wherein at least one of said ocular targeting moieties is an LHRH-receptor antibody.
13. The composition of claim 1 , wherein at least one of said plurality of transferrin-receptor-targeting moieties is transferrin.
14. The composition of claim 1 , wherein at least one of said plurality of transferrin-receptor-targeting moieties is a transferrin-receptor antibody.
15. A method of treating or preventing ophthalmic disorders in a mammal, comprising administering to the eye a composition capable of delivering a therapeutically effective amount of a therapeutic agent, wherein said composition comprises a plurality of poly(lactide) carrier particles comprising a therapeutically effective amount of a therapeutic agent, a plurality of ocular targeting moieties conjugated to the outer surface of said carrier particles, wherein said ocular targeting moieties are LHRH-receptor targeting moieties, and a plurality of transferrin-receptor-targeting moieties conjugated to the outer surface of said carrier particles, and wherein the therapeutic agent and the ocular targeting moieties are not the same.
16. The method of claim 15 , wherein said administration is topical administration.
17. The method of claim 15 , wherein said administration is by injection.
18. The method of claim 15 , wherein said ophthalmic disorder is a disorder of the anterior segment of the eye.
19. The method of claim 18 , wherein said disorder of the anterior segment of the eye is selected from the group consisting of dry eye, glaucoma, allergic conditions, inflammatory conditions of the anterior segment and cornea, allergic conditions of the anterior segment and cornea, infectious conditions of the anterior segment and cornea, and corneal angiogenesis.
20. The method of claim 15 , wherein said ophthalmic disorder is a disorder of the posterior segment of the eye.
21. The method of claim 20 , wherein said disorder of the posterior segment of the eye is selected from the group consisting of macular degeneration, diabetic retinopathy, inflammatory conditions of the posterior segment, infectious conditions of the posterior segment, neurodegenerative disease, and vascular disease of the posterior segment.
22. The method of claim 15 , wherein said administration is intravenously.