The work is devoted to study of new nanostructural photosensitizer Octasens based on micellar form of Zinc 4,5-octakis(decylthio)-3,6-octachlorphthalocyanine with absorption maximum at 728 nm. Photosensitizer shows selective accumulation in tumors and provides efficient (more than 83%) inhibition of growth of model tumor.
The purpose of present work was preparation of lyophilized liposomal form of mitoxantrone and its standardization. Liposomes were prepared by reverse evaporation method using phospholipids, lipid-grafted polyethylenglycol and cholesterol with their subsequent loading by mitoxantrone based on the formation of ammonium gradient between the internal and external aqueous phase of liposomes. The chemical and pharmaceutical researches were carried out. The efficacy of mitoxantrone encapsulation in liposomes was 95± 3%, the diameter of vesicles was 141±6 nm. The lyophilized liposomal form of mitoxantrone was prepared and it was stable at storage.
The directed delivery anticancer drugs by immunoliposomal transport systems are one of the ways to realize the target strategies. The MUC-1 antigen expressed on the surface of the most common human cancer is one of the attractive targets for directed delivery of anticancer drugs. The purpose of present work was preparation anti-MUC-1 immunoliposomal construction loaded with doxorubicin and assessment their specific activity in vitro. Immunoliposomal constructions were prepared by reverse evaporation method using phospholipids, lipid-grafted PEG cholesterol and activated PNp-PEG3000 lipid with their subsequent loading by doxorubicin based on the formation of ammonium gradient between the internal and external aqueous phase of liposomes. The efficacy of doxorubicin encapsulation in immunoliposomes was 87-94 % the diameter of vesicles was 140 ± 5 nm. The high level of аntigen specificity and cytotoxic activity of this construction was obtained.
In this study we have examined the activity of various drug formulations of mitoxantrone in vitro and in vivo. Our in vitro data indicated that the liposomal mitoxantrone was not as effective as free form of drug. However, in vivo animal models Ca-755 and P-388 the effect of liposomal form of mitoxantrone was much more promising in compare with free form of drug. The mitoxantrone formulations were injected into mice at a therapeutic dose regimen with a 96 h interval. The overall results of this study suggest that liposomal mitoxantrone increases the bioavailability of a preparation and reduces the dose for about 6-fold.
The MUC1 antigen is one of the targets for directed delivery of anticancer drugs. It is long known that overexpression of this antigen participates at the activation of program cell death in most malignant cells including breast cancer and ovarian cancer cells. The directed delivery of immunoliposomal anticancer drugs carrying monoclonal antibodies raised against this antigen is one of the ways to realize the target strategies to MUC1 antigen. We have developed the breast and ovarian cancer models based on transplantation of T47D or SKOV3 cells into immunodeficient mice Balb/c nude to examine the effect of anticancer drugs. We have characterized these two models by immunofluorescent staining of MUC1 expression in the experimental animal models. We have also followed the expression of angiogenic markers, depending on the duration of passages in mice. The stable expression of MUC1 antigen in both models was observed in all of 5 passages as well as the high angiogenic activity of tumors., Based on data obtained, we suggest that these two models allow to perform systemic therapy of tumor and could be recommended to screen anticancer activity of immunoliposomal drugs directed against to MUC1 antigen.
Current work was performed to estimate the influence of liposomal size distribution on the level and selectivity of accumulation of long-wavelength photosensitizer Tiosens (liposomal form of aluminium hydroxide phenylthiophthalocyanine) in tumor. Tiosens liposome dispersions were prepared using classic Bangham procedure. Particle size was reduced and unified using Avanti Mini-Extruder equipped with Nucleopore membranes and high-pressure homogenizer «Donor-1». Liposomal size distribution was determined by means of laser correlation spectroscopy. Dynamics and selectivity of Tiosens accumulation in Erlich tumor were measured in vivo using fluorescence spectroscopy. It was shown that level and selectivity of accumulation of liposome-encapsulated drug is determined mostly by content of small-sized fractions, while fractions of larger size are quickly cleared from blood by RES and not contribute in photosensitizer accumulation.
The aim of this paper is to examine the effect of sterically stabilized liposomal form and solution of the photosense in response to alteration of wavelengths of a laser irradiation on photodynamic therapy of mice with breast adenocarcinoma Са 755. The effectiveness of photodynamic therapy was examined at wavelengths 671, 678, 687 nm. The results obtained indicate that the best therapeutic effect was at 671 and 687 nm despite the fact that the maximun absorption was estimated at 678 nm.
The article is devoted to the theoretical estimation and analysis of relationship between optical absorption of photosen-sitizer in biological tissue under treatment and the dose of light required to efficiently affect the deepest layers of tumor during PDT. It is shown that high that the therapeutic irradiation duting PDT may be efficiency used in a spectral range of maximum transparency if biological tissue. On the other hand, it is shown that while increase of sensitizers absorption in tumor, e.g. by increase of its concentration, does enhance the efficiency of use of light up to some level, further increase of it might decrease the efficiency due to shadowing of deeper layers of the tumor by highly sensitizer upper layers.