G. A. Meerovich

Efficiency and Pharmacokinetics of Photosense: A New Liposomal Photosensitizer Formulation Based on Aluminum Sulfophthalocyanine

The photodynamic activity and pharmacokinetics of a new liposomal form (LF) of the sensitizer Photosense based on aluminum sulfophthalocyanine salts have been studied in comparison to those of the standard form (SF) representing a 0.2% aqueous solution of the parent substance. The effective therapeutic doze of the LF of Photosense in mice bearing Ehrlichs tumor was 1 mg/kg, which is four times as small as the effective dose of the SF. The selectivity of accumulation in the tumor tissue 24 h after administration for the LF of Photosense was 1.5 times higher than for the SF. The drug accumulation in skin (determined by the fluorescence intensity) on the 7th days of experiment for the LF of Photosense was 1.6 times lower than for the SF. The pharmacokinetics of the LF of Photosense in mice without tumors significantly differs from the behavior of the SF.

Hydroxyaluminium Tetra-3-Phenylthiophthalocyanine is a New Effective Photosensitizer for Photodynamic Therapy and Fluorescent Diagnosis

We studied the possibility of using liposomal forms of hydroxyaluminium tetra-3-phenylthiophthalocyanine as a near infrared band photosensitizer. Experiments on mice with solid Ehrlich tumor and subcutaneously transplanted P-388 leukemia revealed high selectivity of accumulation of the photosensitizer in tumors in comparison with normal tissues and high photodynamic activity of the preparation. This photosensitizer can be used as the basis for creating an effective preparation for photodynamic therapy and fluorescent diagnosis.

Comparative studies in vivo of free and liposomal forms of photosensitizer on a base of hydrophilic derivative of chlorin e6

This work presents the results of a comparative study in vivo of photosensitizer based on hydrophilic derivative of chlorin e6 upon systemic administration in commercially available aqueous solution and liposomal form. It is demonstrated that newly developed liposomal form provides more selective accumulation of photosensitizer in tumor tissue and efficiency of antitumor action, as well as achieving an enhanced storage stability in comparison to the original form.

Study of Phthalocyanine Derivatives as Contrast Agents for Magnetic Resonance Imaging

The work is devoted to study of new prototype contrasting agents for magnetic resonance imaging on a base of manganese and gadolinium sulphophthalocyanines. Candidate complexes were shown to possess the R1 molar relaxivity values comparable or exceeding ones for commercially available clinical contrast agents such as Magnevist. Intravenous administration of aqueous solution of studied complexes resulted in significant enhancement of contrast of C6 glioma imaging under T1-weighted protocol, allowing to consider them as perspective for further development. Near infrared photosensitizers based on nanoparticular forms of phthalocyanine derivatives.

Near-infrared photosensitizers based on nanostructured forms of phthalocyanine derivatives

The research is devoted to development and study of photosensitizers on a base of injectable nanoparticular formulations of phthalocyanine derivatives absorbing at long wavelength (near-infrared) range of 710–740 nm: Thiosens [liposomal form of aluminum hydroxide 1,8,15,22-tetrakis(phenylsulfanyl)phthalocyanine] and Octasens [polymeric micellar form of zinc 1,4,8,11,15,18,22,25-octachloro-2,3,9,10,16,17,23,24-octakis-(decylsulfanyl)phthalocyanine based on domestic poloxamer Emuxol-268]. Experiments have shown that the photosensitizers under study show high selectivity of accumulation and prolonged retaining at high concentration in tumor, relatively fast clearance from normal tissue and high therapeutic efficiency of photodynamic treatment on model tumors.

Mesoporous Silica Particles as Nanocontainers for Phthalocyanine Photosensitizers: Estimation of Efficiency in In Vivo Experiments

The template synthesis of mesoporous silica nanoparticles with predetermined size and porous structure is carried out. Water-soluble photosensitizer Photosens is used to study the possibility of applying such particles as containers for photosensitizers of a phthalocyanine series. In vivo experiments have shown that the application of such nanocontainers for the delivery of Photosens to a tumor makes it possible to improve the efficiency of fluorescence diagnostics and the photodynamic therapy of cancer.

Study of manganese bacteriopheophorbide as a potential contrast agent for magnetic resonance tomography

The use of manganese bacteriopheophorbide characterized by a high relaxation capacity and selectively accumulating in the tumor as a contrast agent for magnetic resonance tomography significantly improves tumor contrasting against the background of normal tissues. The pharmacokinetics and selectivity of accumulation were studied by diffuse reflection spectroscopy.

Aluminium hydroxide tetra-3-phenylthiophthalocyanine as new photosensitizer for photodynamic therapy and fluorescent diagnostics

This work is devoted to investigation of possibility to use the liposomal form of aluminium hydroxide tetra-3-phenylthiophthalocyanine as photosensitizer of near-infrared range. Aluminium hydroxide tetra-3-phenylthiophthalocyanine has shown high selectivity of accumulation in tumor comparing to normal tissue of mice as well as high photodynamic efficiency on mice bearing Erlich tumor (ELD) and lympholeucosis P-388. This compozition can be used to develop new effective photosensitizer for photodynamic therapy and fluorescent diagnostics.

In vivo evaluation of accumulation of sensitizers for oncological diagnostics and therapy using the method of diffuse reflectance spectroscopy

The article is devoted to in vivo investigations of absorption in biological tissue sensitized by preparations used for diagnostics and therapy of tumors. Efficiency of method of difhse reflectance spectroscopy for in vivo evaluation of accumulation of sensitizers is demonstrated.

New efficient near-IR photosensitizer based on bacteriochlorin p N-methoxycycloimide oxyme methyl ester

This work is devoted to investigation of new photosensitizer Bacteriochlorin p N-methoxycycloimide oxyme methyl ester (BchlpOx-NOMe). Investigations of photosensitizer in vivo and experimental PDT were performed on animals bearing intramuscularly inoculated Erlich tumor and B16 melanoma. Characteristic absorption maximum of BchlpOx-NOMe around 795 nm is within the range of minimum intrinsic absorption of biological tissue. Dynamics and selectivity of sensitizer accumulation in tumor and normal tissue were estimated from spectra of absorption of sensitized tissue in vivo. The investigation has shown that the optimum time range to start PDT irradiation of tumor is 10-30 min after administration. Photosensitizer has shown high photodynamic efficiency of relatively large tumors, including high PDT efficiency in preliminary experiments with BDF1 mice bearing B16 melanoma, causing tumor growth inhibition more than 90% and prolongation of lifespan of tumor-bearing animals more than 60%.