Liposomal hypocrellin B as a potential photosensitizer for age-related macular degeneration: pharmacokinetics, photodynamic efficacy, and skin phototoxicity in vivo.

Abstract

Photodynamic therapy (PDT) has been successfully implemented as a treatment for wet age-related macular degeneration (AMD), but very few photosensitizers have been developed for clinical use. Herein, we describe a novel formulation of liposomal hypocrellin B (LHB) that was prepared by high-pressure homogenization. The encapsulation efficiency and PDT efficacy in vitro of this new preparation were found to remain nearly constant over 1 year. Moreover, LHB is rapidly cleared from the blood, with a half-life of 2.319 ± 0.462 h and a very low serum concentration at 24 h after injection. Testing in a rat model of choroidal neovascularization (CNV) showed that leakage of blood vessels in CNV lesions was significantly reduced when LHB PDT was given at a dose of 1 mg kg(-1) along with yellow laser irradiation; the damage to the collateral retina and the retinal pigment epithelium was minimal. Skin phototoxicity assays showed that only two of the 200 mice given a 4 mg per kg dose of LHB experienced an inflammatory reaction in the auricle irradiated at 24 h after dosing. These data collectively indicate that LHB may be a safe and effective photosensitizer for vascular-targeted PDT of AMD.

• Authors: Tinghui Li, Xiaobin Hou, Hong Deng, Jingquan Zhao, Naiyan Huang, Jing Zeng, Hongxia Chen, Ying Gu
• Journal: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology (Photochem Photobiol Sci) Vol. 14 Issue 5 Pg. 972-81 (May 2015) ISSN: 1474-9092 [Electronic] England
• PMID: 25793654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Photosensitizing Agents
• Quinones
• Perylene
• hypocrellin B

Topics

• Animals
• Cell Survival (drug effects, radiation effects)
• Cells, Cultured
• Choroidal Neovascularization
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Ear (pathology)
• Endothelial Cells (drug effects, physiology, radiation effects)
• Female
• Liposomes (chemical synthesis)
• Lung (blood supply)
• Male
• Mice
• Microvessels (drug effects, physiology, radiation effects)
• Organ Size
• Perylene (administration & dosage, analogs & derivatives, chemical synthesis, pharmacokinetics, toxicity)
• Photochemotherapy (methods)
• Photosensitizing Agents (administration & dosage, chemical synthesis, pharmacokinetics, toxicity)
• Quinones (administration & dosage, chemical synthesis, pharmacokinetics, toxicity)
• Rats
• Retina (drug effects, pathology, radiation effects)
• Skin (drug effects, pathology, radiation effects)
• Wet Macular Degeneration (pathology, therapy)