Assessment genotoxicity of photodynamic therapy with phthalocyanine-chlorine-alumi...
| Full text | |
| Author(s): |
Salomao, Gustavo H. A.
[1]
;
Fernandes, Adjaci U.
[2, 3]
;
Baptista, Mauricio S.
[3]
;
Tardivo, Joao Paulo
[1]
;
Gianssante, Stella
[2, 3]
;
Veridiano, Juliana Mora
[1]
;
Toledo, Olga Maria S.
[1]
;
Petri, Giuliana
[1]
;
Christofolini, Denise Maria
[1]
;
Correa, Joao Antonio
[1]
Total Authors: 10
|
| Affiliation: | [1] Fac Med ABC, Sao Paulo - Brazil
[2] Univ Anhembi Morumbi, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Quim, Dept Biochem, AV Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Bioorganic & Medicinal Chemistry Letters; v. 28, n. 10, p. 1870-1873, JUN 1 2018. |
| Web of Science Citations: | 1 |
| 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 MCHCChlorin 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. (C) 2018 Elsevier Ltd. All rights reserved. (AU) | |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support type: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |