title: 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: Department of Dermatology, 309 Hospital of PLA, No. 17, Heishanhu Road, Beijing 100091, China. drlitinghui@163.com.
authors: Tinghui
authors: T
authors: Li
authors: Xiaobin
authors: X
authors: Hou
authors: Hong
authors: H
authors: Deng
authors: Jingquan
authors: J
authors: Zhao
authors: Naiyan
authors: N
authors: Huang
authors: Jing
authors: J
authors: Zeng
authors: Hongxia
authors: H
authors: Chen
authors: Ying
authors: Y
authors: Gu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D020256:Choroidal Neovascularization; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004423:Ear / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D008081:Liposomes / Q000138:chemical synthesis; D008168:Lung / Q000098:blood supply; D008297:Male; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009929:Organ Size; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D011809:Quinones / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D057135:Wet Macular Degeneration / Q000473:pathology / Q000628:therapy*
chemical_list: D008081:Liposomes; D017319:Photosensitizing Agents; D011809:Quinones; D010569:Perylene; C064522:hypocrellin B