Photobac derived from bacteriochlorophyll-a shows potential for treating brain tumor in animal models by photodynamic therapy with desired pharmacokinetics and limited toxicity in rats and dogs.

Photobac is a near infrared photosensitizer (PS) derived from naturally occurring bacteriochlorophyll- a, with a potential for treating a variety of cancer types (U87, F98 and C6 tumor cells in vitro). The main objective of the studies presented herein was to evaluate the efficacy, toxicity and pharmacokinetic profile of Photobac in animals (mice, rats and dogs) and submit these results to the United States Food and Drug Administration (US FDA) for its approval to initiate Phase I human clinical trials of glioblastoma, a deadly cancer disease with no long term cure. The photodynamic therapy (PDT) efficacy of Photobac was evaluated in mice subcutaneously implanted with U87 tumors, and in rats bearing C6 tumors implanted in brain. In both tumor types, the Photobac-PDT was quite effective. The long-term cure in rats was monitored by magnetic resonance imaging (MRI) and histopathology analysis. A detailed pharmacology, pharmacokinetics and toxicokinetic study of Photobac was investigated in both non-GLP and GLP facilities at variable doses following the US FDA parameters. Safety Pharmacology studies suggest that there is no phototoxicity, cerebral or retinal toxicity with Photobac. No metabolites of Photobac were observed following incubation in rat, dog, mini-pig and human hepatocytes. Based on current biological data, Photobac-IND received the approval for Phase-I human clinical trials to treat Glioblastoma (brain cancer), which is currently underway at our institute. Photobac has also received an orphan drug status from the US FDA, because of its potential for treating Glioblastoma as no effective treatment is currently available for this deadly disease.

Bacteriochlorophyll a, and its derivatives: chemistry and perspectives for cancer therapy.

The review summarizes the chemistry of the third generation of photosensitizers, namely, the derivatives of natural bacteriochlorophyll a, for photodynamic treatment of cancer. The compounds of this class strongly absorb light at lambda=770-850 nm. This unique property opens new therapeutic opportunities due to deeper tissue penetration of light, thereby increasing the photodamage for tumor eradication. Analyzed are the modifications of bacteriochlorophyll a, that improve physico-chemical characteristics of compounds and enhance accumulation in tumors. Focusing on the delivery of photosensitizers to the tumor site and to specific intracellular compartments, we describe the conjugates of bacteriochlorophyll a, derivatives with carbohydrate and protein carriers. Boronated bacteriochlorins can be used in both photodynamic and boron neutron capture therapy.

Photobiological and ultrastructural studies of nanoparticles of poly(lactic-co-glycolic acid)-containing bacteriochlorophyll-a as a photosensitizer useful for PDT treatment.

The interaction of polymeric nanoparticles formulated from the biodegradable polymer poly(DL-lactide-co-glycolide) loaded with bacteriochlorophyll-a was studied in homogeneous solution and in vitro in the presence of a macrophage cell line (P388-D1-ATCC). Photodynamic therapy (PDT) activity after different laser doses also was investigated. Scanning electron microscopy analysis of cell phagocyte nanoparticles showed that after 30 min of incubation most of the nanoparticles are in a clear adhesion process to the cell surface. The majority of nanoparticles became phagocytic after 2 hr of incubation time. After laser irradiation of the dye-containing system a total photodamage by nanoparticle phagocyte cells was observed and the cell survival was quantified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Our results indicate that polymeric nanoparticles work as an efficient drug delivery system for PDT drugs. This approach can be widely used for many other hydrophobic photosensitizers with higher aggregation tendency in neoplastic cell treatment.