A new Chlorin formulation promotes efficient photodynamic action in choriocapillaris of rabbit's eyes. Issue 10 (1st June 2018)

• Record Type: Journal Article
• Authors: Salomao, Gustavo H.A.; Fernandes, Adjaci U.; Baptista, Mauricio S.; Tardivo, João Paulo; Gianssante, Stella; Veridiano, Juliana Mora; Toledo, Olga Maria S.; Petri, Giuliana; Christofolini, Denise Maria; Correa, João Antonio
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 10(2018)
• Page Start: 1870
• Page End: 1873
• Publication Date: 2018-06-01
• Subjects: Age-related macular degeneration -- Choroidal vascular diseases -- Choroidal neovascularization -- PDT -- Liposome -- Photosensitizer -- Chlorin; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.04.007
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Synthesis of MCHC-Chlorin is reported with 92% yield. The liposome formulation of MCHC-Chlorin targets the choroidal vasculature. Tests showed efficient occlusion of choriocapillary vessels in rabbit's eyes. Sclera and retina are preserved. The new formulation presents great potential for the treatment of choroidal diseases. Abstract: Age-related macular degeneration (AMD) as well as other choroidal diseases, demand novel therapeutic methods. Photodynamic therapy (PDT), which uses light and photosensitizer (PS) to cause specific vascular occlusion in the macula, is an interesting alternative. The only drug approved for the PDT treatment of AMD (Verteporfin) has a natural tendency to aggregate, demanding an expensive separation procedure during purification. We report a novel and affordable PS that is intrinsically protected against aggregation, the Monomeric Chlorin at High Concentration ( MCHC -Chlorin), whose liposomal formulation was developed to provoke effective photodynamic action on the choroidal vasculature. Our report starts by stablishing the conditions to allow the efficient synthesis of MCHC -Chlorin in high yields (92%). We then tested the light stimulated occlusion of choriocapillary vessels in rabbit's eyes induced by the two MCHC-Chlorin isomers, which are directly obtained from the synthetic route. The PS formulation was infused in the rabbit's ear vein and eyes were immediately irradiated at 650 nm. Indirect ophthalmoscopy, fundus photography, fluorescein angiography and histopathological evaluations were used to evaluate levels of photo-thrombosis and collateral damage. Choriocapillary occlusion was achieved in all treated rabbits' eyes, while retina and sclera were completely preserved. There was no photochemical reaction in none of the eyes that received LASER without PS. Both MCHC-Chlorin isomers were separately tested and exhibited similar positive results with no systemic toxicity. Therefore, PDT occurred equally well in all treated eyes and none of the controls showed any effect in the ophthalmological exams. MCHC-Chlorin offers great potential and should be further studied as an alternative drug for choroidal diseases.