Suppression of choroidal neovascularization by intravitreal injection of liposomal SU5416.

Abstract

OBJECTIVE:

To clarify whether use of angiogenic vessel-homing peptide, Ala-Pro-Arg-Pro-Gly (APRPG)-modified liposomes encapsulating 3-([2,4-dimethylpyrrhol-5-yl] methylidenyl)-indolin-2-one (SU5416), an angiogenesis inhibitor, can inhibit the development of experimental choroidal neovascularization (CNV) in rats.

METHODS:

Liposomes were prepared using the thin-film hydration method. To set up the rat experimental CNV model, intense fundus laser photocoagulation at 6 spots per eye was performed on pigmented rats. After photocoagulation, the rats were divided into 4 groups (6 rats in each group): an APRPG-liposomal SU5416 treatment group and control groups treated with a balanced salt solution, APRPG liposomes, or soluble SU5416. Each rat received a single intravitreal injection immediately after the injury. One week or 2 weeks after laser injury, the extent of CNV was evaluated by perfusion with high-molecular-weight fluorescein isothiocyanate-dextran.

RESULTS:

Two weeks after injection, the CNV area was significantly (P < .05) smaller in the APRPG-liposomal SU5416-treated group compared with the CNV area in the balanced salt solution-and APRPG liposome-treated groups.

CONCLUSION:

Liposomes modified by APRPG and encapsulating SU5416 constitute a potential drug formulation for CNV treatment that would require only a single intravitreal injection.

CLINICAL RELEVANCE:

This liposomal delivery may enable the sustained release of small molecules and be a new treatment modality for CNV.

• Authors: Miki Honda, Tomohiro Asai, Takuya Umemoto, Yoshihiko Araki, Naoto Oku, Minoru Tanaka
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 129 Issue 3 Pg. 317-21 (Mar 2011) ISSN: 1538-3601 [Electronic] United States
• PMID: 21402988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Carbocyanines
• Dextrans
• Fluorescent Dyes
• Indoles
• Liposomes
• Oligopeptides
• Pyrroles
• alanyl-prolyl-arginyl-prolyl-glycine
• fluorescein isothiocyanate dextran
• 3,3'-dioctadecylindocarbocyanine
• Semaxinib
• Protein-Tyrosine Kinases
• Fluorescein-5-isothiocyanate

Topics

• Angiogenesis Inhibitors (administration & dosage)
• Animals
• Carbocyanines
• Choroidal Neovascularization (diagnosis, drug therapy)
• Dextrans
• Disease Models, Animal
• Fluorescein-5-isothiocyanate (analogs & derivatives)
• Fluorescent Dyes
• Indoles (administration & dosage)
• Intravitreal Injections
• Liposomes
• Male
• Oligopeptides (chemistry)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Pyrroles (administration & dosage)
• Rats
• Rats, Inbred BN