pHOTODyNAMIc EffIcAcy Of TOpIcAL AppLIcATION Of cHLORIN e6-pOLyvINyL pyRROLIDONE cOMpLEx IN TuMOR-bEARINg RATS

Y Istoтin, T Laptsevich, S Bizyuk, E Alexandrova
unpublished
Photodynamic therapy �P�T�� is �ased on the a�ility of specific su�stances�� the so-called photosensitizers �PS�� to accumulate selectively in tumor tissue �eing injected i. v. and to �e photoactivated with light of specific wavelength to generate singlet oxygen and free radicals�� which cause destruction of tumor cells [1�� �]. The main disadvantage of the most photosensitizers recently used for P�T in clinics is prolonged skin photosensitivity. �uring ���� months following treatment with
more » ... treatment with Photoheme or Photosense �Russia�� and during 1 week following treatment with Photolon �Belarus���� patients should not �e exposed to direct sunlight etc. to prevent phototoxic reactions such as hyperemia�� edema and �urn of open sites of a �ody. Creation of new PSs and appropriate lasers is not the only way to enhance the efficacy of P�T. New methods of local application of PS are �eing developed ena�ling to reduce the side effects of treatment and to lower its cost. So�� it has �een shown that local application of the mono-L aspartyl chlorin e�� or 5-aminolevulinic acid�� a precursor of endogenic PS protoporphyrin IX�� promotes considera�ly higher accumulation of PS in tumor tissue�� in comparison with normal tissues [��� 4]. The P�T using local application of ��% cream of 5-aminolevulimic acid for superficial malignant skin tumors has �een carried out [5] . The photosensitizer of the second generationchlorin e�� was reported to have significant efficacy in killing cancer cells in vitro and in vivo. P�T with chlorin e�� -polyvinyl pyrrolidone complex �Photo-lon�� administrated intravenously is a highly effective method for treatment of the patients with skin cancer and intradermal metastases of melanoma and �reast cancer. O�jective effect of treatment in such patients has �een achieved in 1��% of cases [��]. The aim of this study was to develop a technique and to investigate antitumor efficiency of P�T using Photolon in the form of � or 5% ointment. The investigation tasks were: to develop a technique of topical application of Photolon ointment in tumor-�earing rats; to study the accumulation of � and 5% Photolon ointment in normal and tumor tissues of la�oratory animals; to evaluate the efficacy of P�T with different concentrations of Photolon ointment applied for different periods -from 15 min to 5 h. MATERIALS AND METHODS Experimental animals and tumors. Eighty white randomly �red rats o�tained from the vivarium of the N.N. Alexandrov Research Institute of Oncology and Medical Radiology �Minsk�� Belarus�� were used. The animals received a standard diet and had permanent access to water. SM-1 experimental rat fi�rosarcoma was o�tained from the tumor strains collection of the N.N. Blokhin Cancer Research Centre of the Russian Academy of Medical Sciences �Moscow�� Russia�� and was passed �y serial transplantation. For experiments tumor homogenate was implanted su�cutaneously into the inguinal region �y the injection of �.5 ml of 1�% tumor cell suspension in the Hanks' solution. Before the treatment the animals were anesthetized with droperidol �5 mg/kg�� and fentanil ��.�5 mg/kg�� and restrained. All manipulations were carried out according to the international and scientific ethic standards of the quality of planning and carrying out of animal investigations�� specifically�� according to "Methodic instructions for carrying out preclinical investigations of pharmacokinetics of pharmacologic su�stances and drugs" presented in the "Guide on experimental �preclinical�� study of new pharmacologic su�stances" // Health Ministry of Russian Federation�� Aim: To evaluate the antitumor efficacy of �hoto�ynamic thera�y �ith ointment form of chlorin e�� �� �olyvinyl �yrroli�one com�le��� �hoto�ynamic thera�y �ith ointment form of chlorin e�� �� �olyvinyl �yrroli�one com�le��� �ith ointment form of chlorin e�� �� �olyvinyl �yrroli�one com�le��� �� �olyvinyl �yrroli�one com�le��� �� �olyvinyl �yrroli�one com�le��� Methods: 2 or 5% chlorin e�� ointment �as a��lie� on the surface of rat ����� tumor for ��5 min �� 5 h�� an� then tumors �ere score� on the surface of rat ����� tumor for ��5 min �� 5 h�� an� then tumors �ere score� on the surface of rat ����� tumor for ��5 min �� 5 h�� an� then tumors �ere score� for �hotosensitizer accumulation an� tissue �amage in�uce� by laser irra�iation�� Results: �electivity of chlorin e�� accumulation in tumor tissues consi�erably increases �hen �hotosensitizer �as a��lie� to�ically com�are� �ith intravenous a�ministration�� �ntitumor �hotosensitizer �as a��lie� to�ically com�are� �ith intravenous a�ministration�� �ntitumor �as a��lie� to�ically com�are� �ith intravenous a�ministration�� �ntitumor efficacy of �hoto�ynamic thera�y using to�ical a��lication of chlorin e�� �� �olyvinyl �yrroli�one com�le� is �ust as high as u�on intra� �hoto�ynamic thera�y using to�ical a��lication of chlorin e�� �� �olyvinyl �yrroli�one com�le� is �ust as high as u�on intra� using to�ical a��lication of chlorin e�� �� �olyvinyl �yrroli�one com�le� is �ust as high as u�on intra� venous a�ministration of the �re�aration�� Conclusion: The level of tissue accumulation of chlorin e�� �� �olyvinyl �yrroli�one com�le� �� �olyvinyl �yrroli�one com�le� �� �olyvinyl �yrroli�one com�le� a�ministere� in ointment form allo�s to carry out fluorescence �iagnosis an� PDT of su�erficially localize� malignant tumors�� Key Words: �hoto�ynamic thera�y�� �hotosensitizers�� chlorin e���� rat sarcoma ������ rat sarcoma ������ sarcoma ������
fatcat:73qo2vmw2zdv5gk4ylhv6i3nbm