Daiana K. Deda

A new micro/nanoencapsulated porphyrin formulation for PDT treatment

The highly hydrophobic 5,10,15-triphenyl-20-(3-N-methylpyridinium-yl)porphyrin (3MMe) cationic species was synthesized, characterized and encapsulated in marine atelocollagen/xanthane gum microcapsules by the coacervation method. Further reduction in the capsule size, from several microns down to about 300-400 nm, was carried out successfully by ultrasonic processing in the presence of up to 1.6% Tween 20 surfactant, without affecting the distribution of 3MMe in the oily core. The resulting cream-like product exhibited enhanced photodynamic activity but negligible cytotoxicity towards HeLa cells. The polymeric micro/nanocapsule formulation was found to be about 4 times more phototoxic than the respective phosphatidylcholine lipidic emulsion, demonstrating high potentiality for photodynamic therapy applications.

Resolution of isomeric multi-ruthenated porphyrins by travelling wave ion mobility mass spectrometry.

The ability of travelling wave ion mobility mass spectrometry (TWIM-MS) to resolve cationic meta/para and cis/trans isomers of mono-, di-, tri- and tetra-ruthenated supramolecular porphyrins was investigated. All meta isomers were found to be more compact than the para isomers and therefore mixtures of all isomeric pairs could be properly resolved with baseline or close to baseline peak-to-peak resolution (R(p-p)). Di-substituted cis/trans isomers were found, however, to present very similar drift times and could not be resolved. N(2) and CO(2) were tested as the drift gas, and similar α but considerably better values of R(p) and R(p-p) were always observed for CO(2).

Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum

UNLABELLED Several synthetic metallated protoporphyrins (M-PPIX) were tested for their ability to block the cell cycle of the lethal human malaria parasite Plasmodium falciparum. After encapsulating the porphyrin derivatives in micro- and nanocapsules of marine atelocollagen, their effects on cultures of red blood cells infected (RBC) with P. falciparum were verified. RBCs infected with synchronized P. falciparum incubated for 48 h showed a toxic effect over a micromolar range. Strikingly, the IC50 of encapsulated metalloporphyrins reached nanomolar concentrations, where Zn-PPIX showed the best antimalarial effect, with an IC50=330 nM. This value is an 80-fold increase in the antimalarial activity compared to the antimalarial effect of non-encapsulated Zn-PPIX. These findings reveal that the incubation of P. falciparum infected-RBCs with 20 μM Zn-PPIX reduced the size of hemozoin crystal by 34%, whereas a 28% reduction was noticed with chloroquine, confirming the importance of heme detoxification pathway in drug therapy. FROM THE CLINICAL EDITOR In this study, synthetic metalloporphyrins were tested as therapeutics that target Plasmodium falciparum. The IC50 of encapsulated metalloporphyrins was found to be in the nanomolar concentration range, with encapsulated Zn-PPIX showing an 80-fold increase in its antimalarial activity compared to the non-encapsulated form.

Nanotechnology, Light and Chemical Action: an Effective Combination to Kill Cancer Cells

Photodynamic therapy (PDT) is a minimally invasive and effective procedure for treatment of cancer, based on the combination of a drug (photosensitizer, PS), light (visible or near-infrared, NIR) and induced local formation of reactive oxygen species (ROS) and radicals. Despite its less significant side effects as compared with conventional therapies, many efforts still are been focused on enhancing the selectivity and efficiency of PSs and thus, of commercial drugs. Nanotechnology is providing many interesting possibilities and tools to develop drug delivery systems (DDS) and multifunctional platforms for therapy, diagnosis and theranostics. More recently, their effectiveness against tumor cells and tissues is being improved by combining the synergic effects of chemotherapeutic agents and other therapies, making them more interesting therapeutic alternatives. Accordingly, this review is focused on the recent contributions of nanotechnology on PDT, converging to the development of DDSs and multifunctional systems and their application for cancer therapy.

Correlation of photodynamic activity and singlet oxygen quantum yields in two series of hydrophobic monocationic porphyrins

The photodynamic properties of eight hydrophobic monocationic methyl and ruthenium polypyridine complex derivatives of free-base and zinc(II) meso-triphenyl-monopyridylporphyrin series were evaluated and compared using HeLa cells as model. The cream-like polymeric nanocapsule formulations of marine atelocollagen/xanthan gum, prepared by the coacervation method, exhibited high phototoxicity but negligible cytotoxicity in the dark. Interestingly, the formulations of a given series presented similar photodynamic activities but the methylated free-base derivatives were significantly more phototoxic than the respective ruthenated photosensitizers, reflecting the higher photoinduced singlet oxygen quantum yields of those monocationic porphyrin dyes.

Strategies for Development of Antimalarials Based on Encapsulated Porphyrin Derivatives

Despite the efforts in controlling the parasite and infection, and the significant progress achieved in recent years in its treatment, malaria is still prevalent in many regions and out of control in others. The repertoire of alternatives to fight malaria is being expanded, not only by designing new drugs but also by developing improved drug delivery systems able to enhance the antimalarial efficiency of conventional and new drugs. Among the new drugs that have been investigated, several publications report the use of porphyrin derivatives as antimalarials but their efficiency is contradictory. The low activity of porphyrins seems to be associated with low dispersibility and bioavailability. In this respect, Nanotechnology can provide efficient solutions to enhance bioavailability and delivery of conventional and new antimalarials, in order to assure high enough efficiency levels to inactivate the parasite. Thus, in this review we highlight the use of drug delivery systems for conventional and new antimalarials and we propose the encapsulation of porphyrins as a promising alternative for development of anti-malarial formulations.

REPLY to Nanomedicine: NMB, 2015; 11:1035

The observations raised by Somsri Wiwanitkit and Viroj Wiwanitkit concerning our recent report about the encapsulation of metalloporphyrins and their effect on human malaria parasite Plasmodium falciparum highlighted the increasing concern in finding new and safe antimalarial therapies and allow an opportunity to better clarify some aspects of our work. It is well known that one of the effects of chloroquine treatment is to impair the hemozoin formation. In our experiments comparing the hemozoin area in living red blood cells (RBC) infected with P. falciparum, we have confirmed that 20 μM of Zn-PPIX had a similar effect as 1 μM chloroquine on hemozoin growth inhibition after 2 hours incubation. Under these conditions, no relevant differences were observed between Zn-PPIX and chloroquine, however both treatments induced a statistically significant (P b 0.05) decrease on hemozoin area when those groups are compared with a control group treated with DMSO only, as shown in figure and methods section (a full comparison between all groups for this experiment is shown on Table 1). In fact, our work confirmed the results previously obtained by Martiney et al listed as reference 8 of the article. The decrease of hemozoin activity by Zn-PPIX reported by