Analysis of Antitumor Activity of the Liposomal Photosensitizer Lipophthalocyan.

We studied specific antitumor activity of a liposomal drug based on tetra-3-phenylthiophthalocyanine aluminum hydroxide (lipophthalocyan) intended for photodynamic therapy. The optimal dose and protocol for photodynamic therapy with lipophthalocyan were chosen in experiments on mice: single intravenous dose of 6 mg/kg with a 5-h interval between administration and laser exposure and irradiation energy density of 400 J/cm2. A wide spectrum antitumor activity of lipophthalocyan was demonstrated in vivo for various transplantable mouse tumors (Lewis lung epidermoid carcinoma, S37 sarcoma, and colon adenocarcinoma AKATOL). The results show the possibility of using lipophthalocyan for photodynamic therapy of tumors of surface localization (skin and mucosa tumors).

Comparative Analysis of Bioactivity of the Russian-Made Antitumor Substances of the Nitrosourea Group.

We performed an in vivo comparative study of activity of three substances of the nitrosourea group produced in Russia. All substances demonstrated high antitumor activity against various solid and leukemic tumors. Aranosa significantly enhanced life duration in mice with leukemia (by 65-194%) and inhibited the growth of solid tumors (by 49-99.6%). Lisomustine and ormustine showed higher activity than aranose. Single administration of lisomustine increased life span of mice (by 22-114%) and resulted in cure of all animals in four models: lymphoblastic leukemia L-1210, lymphocytic leukemia P-388, Lewis lung carcinoma, and cervical cancer RShM-5. After ormustine treatment, full recovery was observed only in groups with lymphocytic leukemia P-388 and cervical cancer RShM-5. These findings attest to higher activity of lisomustine in the studied models.

Experimental study of combined therapy for malignant glioma.

The efficiency of photodynamic therapy with photosensitizer Tiosens (Russia) was evaluated in mono- and combined therapy of rats with malignant gliomas (glioblastoma 101/8, oligodendroglioma 14-4-9, and C6 glioma). The efficiency of photodynamic monotherapy was not high: the animals died from brain edema developing in tumor tissue and in the adjacent normal cerebral tissue. Pathomorphological studies of tumor tissue detected necrosis and apoptosis, destruction of vessels with hemorrhages, and vascular thrombosis. Combined therapy for malignant gliomas including Tiosens photodynamic therapy and subsequent temodal or lysomustine chemotherapy, was the most effective. In glioblastoma 101/8, combined therapy with lysomustine or temodal led to prolongation of the lifespan by 127 %; 62.5 and 50 % rats were cured, respectively; in oligodendroglioma 14-4-9, animal lifespan was prolonged by 80 and 60 %, with 43 and 45 % rats cured, respectively. Glioma C6 was least sensitive to therapy.

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.

[Study of optical absorption of sensitizers in vivo].

The subject of the paper is study of optical absorption of sensitizers in biological tissue. The study shows that absorbance can be used as a tool that allows studying biodistribution of sensitizers and their interaction with tissue in vivo. The article presents a simple technique of determining biological tissue absorption in vivo, and discusses the results of experimental animal studies of some sensitizers.

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.

[Pharmacological aspects in the development of liposomal medicinal preparations for the internal injection of hydrophobic cytostatics]. / Farmatsevticheskie aspekty razrabotki liposomal'nykh lekarstvennykh form dlia vnutrivennogo vvedeniia hidrofobnykh tsitostatikov.

To improve the action and selectivity of new drugs on tumor cells and the use of currently available pharmaceutical technologies to develop the systems of controlled transport of well-known antitumor compounds is one of the ways of enhancing the efficiency of drug therapy for tumors. The tropicity of steroid hormones to definite organs and tissues makes it possible to use them as specific messengers of alkylating groups to target tissues and tumors. Hormone cytostatics synthesized by this principle have a double mechanism of hormonal and cytotoxic actions. The original Russian water-insoluble hormone cytostatistics testifenon, kortifen, and cytestrol acetate demonstrated local tissue irritation together with high antitumor activity. No rational dosage forms make it possible to conduct clinical trials by parenteral administration. The aim of this paper is to summarize the authors' results of designing hydrophobic antitumor hormone cytostatics. The advantages and disadvantages of different approaches to designing traditional dosage forms and to applying colloid liposomal systems for intravenous administration of water-insoluble agents are shown.

[Results of creating domestic medicinal forms of antineoplastic agents at the N. N. Blokhin Cancer Research Center of the Russian Academy of Medical Sciences]. / Itogi sozdaniia otechestvennykh lekarstvennykh form protivoopukholevykh preparatov v RONTs im. N. N. Blokhina RAMN.

Since there is a rise in morbidity and mortality rates due to malignant neoplasms, their drug therapy along with radiation and surgical methods remains a burning problem of modern medicine. Empirical and rational approaches to searching for new drugs have given rise to cancer agents that are widely used in clinical practice today. By taking into account the chemical and biological features of experimentally chosen active cytostatics, emphasis should be laid on the particular importance of development of effective dosage forms of antitumor substances by conducting chemical analytical, pharmacological engineering, biopharmaceutical, and pharmacokinetic studies. The purpose of the present paper is to assess the retrospective and present status of studies to design dosage forms of cancer drugs in our and foreign countries, and to pool the results of the author's own studies in designing dosage forms of antitumor substances from classes of chloroethylamines, nitrosoalkyl ureas, complex metal compounds, anthracene diones, antibiotics of plant origin, etc.