Preclinical Evaluation of a Novel Water‐soluble Chlorin E₆ Derivative (BLC 1010) as Photosensitizer for the Closure of the Neovessels

Abstract

In the present study, photodynamic activity of a novel photosensitizer (PS), Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.) injection of BLC 1010 into the CAM vasculature, the applicability of this drug for photodynamic therapy (PDT) was assessed in terms of fluorescence pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity. The influence of different PDT parameters including drug and light doses on the photodynamic activity of BLC 1010 has been investigated. It was found that, irrespective of drug dose, an identical continuous decrease in fluorescence contrast between the drug inside and outside the blood vessels was observed. The optimal treatment conditions leading to desired vascular damage were obtained by varying drug and light doses. Indeed, observable damage was achieved when irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v. injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when irradiation with light doses of more than 10 J/cm(2) was performed 1 min after injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large blood vessels. It has been demonstrated that it is possible to obtain the desired vascular occlusion and stasis with BLC 1010 for different combinations of drug and/or light doses.

Vascular regrowth following photodynamic therapy in the chicken embryo chorioallantoic membrane

“…We performed these studies in the CAM since this model has been used for studying and optimizing the effect of PDT on human choroidal (neo)vessels [16, 34–36]. The CAM has been used for studying the application of PDT for eye diseases, including exudative age-related macular degeneration.…”

The chicken chorioallantoic membrane model in biology, medicine and bioengineering

“…In addition, polymeric nanoparticles were also used for this purpose (e.g. poly(lactide-co-glycolide, PLGA or PLA) [118]. An overview of delivery systems tested on the CAM is listed in Table 7.…”

Shifting the Light Activation of Metallodrugs to the Red and Near-Infrared Region in Anticancer Phototherapy

“…TPA closure of blood vessels, which also requires spatial precision, has been demonstrated in a chick embryo model of neovascularization. 114 The local delivery of caged neurotransmitters would also benefit from the inherent spatial precision of TPA, as proposed by Etchenique. 115 For many other phototherapeutic applications, however, irradiation should be performed on a rather large domain (mm 2 to cm 2 ) to make sure all diseased cells are treated.…”