Association of Acenaphthoporphyrins with Liposomes for the Photodynamic Treatment of Leishmaniasis

Abstract

Acenaphthoporphyrins are potential photosensitizers for photodynamic therapy, but their hydrophobicity limits their potential. Liposomes have been widely investigated as delivery vehicles that can transport hydrophobic drugs in biological systems. Here we study the association of acenaphthoporphyrins with liposomes made up of dimyristoyl phosphatidylcholine (DMPC), and to liposomes made up of a mixture of DMPC, cholesterol (Chol) and distearoyl phosphatidylglycerol (DSPG) in a 2:1:0.8 molar ratio to evaluate how liposome composition affects association constants. In liposomes consisting only of DMPC, the smaller monoacenaphthoporphyrin had the largest association constant of 5.5 x 10(4) m(-1) while the larger adj-diacenaphthoporphyrin and opp-diacenaphthoporphyrin (ODP) had smaller association constants at 1.8 x 10(4) and 1.5 x 10(4) m(-1), respectively. The addition of liposomal Chol and DSPG has little effect on the magnitudes of the association constants. Polarization studies show that the acenaphthoporphyrins are driven far into the lipid bilayer to minimize polar-nonpolar interactions. Confocal microscopy confirms that the DMPC liposomes transport the porphyrins into promastigotes of Leishmania tarentolae. The compounds associated with DMPC:Chol:DSPG liposomes are effective in vitro against axenic and intracellular amastigotes of the pathogenic Leishmania panamensis. The effectiveness of the compounds is enhanced upon exposure of cultures to visible light.

Synthesis and Characterization of 5,10,15,20‐Tetrakis(4‐ethylphenyl)porphyrin and (Zn2+, Mn2+, Sn2+, Ni2+, Al3+, V3+)‐Derivatives: Photophysical and DFT study

“…Different porphyrin derivatives have reported PDT activities, specifically the 5,10,15,20‐tetrakis(4‐sulfanatophenyl)‐21H,23H‐porphyrin has shown photochemical efficiency and have been reported as potential for treating carcinoma . Endogenous Protoporphyrin IX (PpIX, 7) was reported as a clinically useful photosensitizer for PDT, Hexaminolevulinate, the n‐hexyl ester of ALA, (HAL, Hexvix®, Cysview®, 10) was approved in 2010 by the US FDA in the diagnosis of bladder cancer, β‐substituted systems such as ethyl and diethyl carbo‐porphyrin, benzoporphyrin and 1–5diaryl‐porohyrin have reported activity against Leishmania (leishmanial parasite) . Nowadays, intensive research is reported on the development of new structures with PDT activity.…”

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

“…For all these reasons, many studies have been focused on exploring different aspects of the behaviour of these carrier systems, as the involved mechanism in cell death, 269,270 or the determination of the most favourable lipidic composition for their performance. [271][272][273] Several groups have reported on PS-liposome hybrid systems for different biomedical purposes, like imaging techniques, 274 and PDT or PDI treatments of different cancerous cell lines or tumours, [275][276][277][278][279][280][281] leishmaniasis, 282,283 Candida albicans, 284 or human chronic periodontitis, 285 among others. More interestingly, liposomes that enable the formulation of more than one active component have recently attracted much attention, as they can be employed as suitable platforms to render more complex third-generation PS (Fig.…”

Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents

“…Lash et al reported the use of alkyl-carbaporphyrin ketal derivatives ( Figure 6) for growth inhibition of Leishmania tarentolae promastigotes by reactive oxygen species generation, such as singlet oxygen and superoxide [110]. Acenaphthoporphyrin derivatives were incorporated into liposomes, due to their low hydrophilicity, thus increasing their bioavailability and photodynamic effects in vitro against axenic and intracellular amastigotes of the pathogenic Leishmania panamensis [111]. The improved solubility consequence of the incorporation of polar groups (e.g., -OH, -COOH, -OMe) to the porphyrin ring periphery tends to enhance their activity against several parasites.…”