NEW PHARMACEUTICAL DOSAGE FORMS USED IN THE TREATMENT OF BREAST CANCER. LIPOSOMES

In order to obtain antineoplastic compounds and innovative formulations, new technologies and testing methods are continuously being developed. Unfortunately, besides cancer cells, chemotherapy also affects normal cells. An option to avoid toxicity is represented by the targeted cancer treatment using novel pharmaceutical dosage forms. Liposomes represent a relatively new pharmaceutical dosage form, used for their many advantages. In this article, the methods of liposomal preparation are mentioned, along with the classification and the latest improvements involving this pharmaceutical form. The bioavailability of conventional liposomes is currently improved by developing photodynamic liposomes, pH or temperature sensitive liposomes and targeted liposomes.

Influence of “Metisevit” feed additive and liposomal preparation “Lipointersil” on the level of vitamins in the blood of bulls at experimental chronic cadmium toxicosis

The article presents the results of research on the effect of feed additive “Metisevit” and liposomal drug “Lipointersil” on the level of vitamins in the blood of bulls in experimental chronic cadmium toxicosis. The research was conducted on the basis of a farm in the village of Ivanivtsi, Zhydachiv district, Lviv region, on 15 bulls of six months of age, Ukrainian black-spotted dairy breed, which were formed into 3 groups of 5 animals each: control and two experimental groups. The bulls of the control group were fed cadmium chloride at a dose of 0.04 mg/kg body weight for 30 days. The bulls of the first experimental group were fed cadmium chloride at a dose of 0.04 mg/kg body weight for 30 days and fed a dietary supplement “Metisevit” at a dose of 0.36 g/kg of feed. The bulls of the second experimental group were fed cadmium chloride at a dose of 0.04 mg/kg body weight for 30 days and fed a dietary supplement “Metisevit” in the above dose. On the first and seventh days of the experiment, bulls of this experimental group were injected intramuscularly with liposomal drug “Lipointersil” at a dose of 5 ml per animal. The composition of the liposomal drug “Lipointersil” includes interferon and milk thistle. In the study of the non-enzymatic part of the antioxidant system of the body of bulls under cadmium load found a decrease in vitamins A and E. The use of feed additive “Metisevit” increased the content of vitamin E in the blood of bulls of the second experimental group by 10.5 % experiment – by 37.9 % relative to the control group. With the additional use of liposomal drug “Lipointersil” in the blood of bulls found a more likely increase in vitamin E levels throughout the experiment than in the second experimental group, where respectively on the 15th and 20th day of the experiment, this figure increased by 35.3 and 55.1 %. The increase in the content of vitamin E in the blood of experimental animals is due to the feeding of the feed supplement “Metisevit”, which contains this vitamin. A similar increase is observed in the study of vitamin A in the blood of bulls of experimental groups. It was found that when using a feed additive and liposomal preparation for bulls, on the 15th day of the experiment the level of vitamin A in the blood of the first experimental group increased by 19.4 %, and in the blood of the second experimental group – by 26.9 % relative to the control group. Thus, the use of feed supplement “Metisevit” and liposomal drug “Lipointersil” for bulls, which are under conditions of cadmium load, helped to increase the non-enzymatic system of antioxidant protection, namely vitamins A and E.

An Underestimated Factor: The Extent of Cross-Reactions Modifying APIs in Surface-Modified Liposomal Preparations Caused by Comprised Activated Lipids

Despite the nowadays available plentitude of strategies to selectively introduce functional surface modification of liposomes, in preclinical research this process is still primarily performed after liposomal preparation utilizing comprised activated phospholipids with functionalized head groups. However, because these activated lipids are present during the liposomal preparation process, they can cross-react with incorporated drugs, especially the particularly often utilized active esters and maleimide groups. Macromolecular drugs, being composed of amino acids, are particularly prone to such cross-reactions due to their often multiple reactive functionalities such as amino and disulfide groups. To demonstrate this impact on the formulation in liposomal surface modification, we assessed the extent of cross-reaction during the liposomal preparation of two activated phospholipids with typically used head group functionalized phospholipids, with the two peptide drugs vancomycin and insulin comprising disulfide and amino functionalities. Both drugs revealed a considerable fraction of covalent modification (estimated 2 to 12%) generated during the liposome preparation process with comprised activated lipids. Modification of the active pharmaceutical ingredients (APIs) was determined by high-resolution mass spectrometric analysis. These findings clearly demonstrate the non-negligibility of potential cross reactions using the post preparation liposomal surface modification strategy in preclinical research.

PROSPECTS OF USING ANTI-IDIOTYPIC ANTIBODIES TO TWO MORPHINE DERIVATIVES IN THE FORM OF LIPOSOMAL FORM FOR THE DEVELOPMENT OF A VACCINE AGAINST OPIATE ADDICTION

The prospects of using liposomes in the creation of a pharmaceutical form of liposomal preparation of antiidiotypic Ab2 antibodies to two derivatives of morphine, which leads to the production of Ab3 antibodies capable of preventing the action of morphine in the body, are considered.

Assessing the Impact of Technological Factors on the Stability of Liposomes the Photosensitizer Phthalocyanine Series

Introduction.Liposomal technologies are widely used in medicine and cosmetology as a delivery system for diagnostic and medicinal products and biologically active substances. The undoubted practical importance at the stage of development of a liposomal preparation is represented by the characteristic and assessment of the sustainability of the obtained product, and special attention is paid to the study of the latter. Essentially, the methods for their preparation affect the stability of liposomes; therefore, the study of the influence of technological factors on the properties of the product at various stages of the preparation of liposomes is very important. This article is devoted to the study of the dependence of the quality of liposomes loaded with a phthalocyanine photosensitizer – thiosens, on the conditions of their production.Aim.Detection of the influence of various technological factors on the stability indicators of the liposomal form of the thiosens photosensitizer.Materials and methods.For this purpose, an analysis of the average size, polydispersity and zeta (ζ) potential of the liposomes of thiosens obtained at the stage of hydration of the lipid film, filtration of the liposomal dispersion, its extrusion, homogenization, ultrasonic treatment, and lyophilization was carried out.Results and discussion.During the preparation of a liposomal preparation, various changes in conditions can be made within the framework of the technological process. At each stage of obtaining a liposomal form, there are many critical points and parameters that must be strictly monitored and controlled. In the course of the work, the influence of technological factors on the stability of liposomal intermediate and finished products was assessed. The conditions of the most effective hydration with the formation of a stable dispersion of multilayer liposomes of thiosens and the optimal method of their grinding have been determined. It was also shown that liposomes formed after rehydration of the lyophilisate are more uniform in size and have the highest ζ-potential value in comparison with non-lyophilized liposomal dispersion.Conclusion.Using the example of a thiosens phthalocyanine photosensitizer liposomes, the influence of various technological factors on the stability of this nanostructure is shown, therefore, the characteristic and assessment of the sustainability of the resulting product according to 3 main indicators – vesicle size, polydispersity index, and ζ-potential are of undoubted practical importance.

Indicators of functional and antioxidant liver status of rats under oxidative stress conditions and on the action of the liposomal drug “Butaselmevit”

The purpose of the work was to study the parameters of the functional and antioxidant state of the liver in rats under conditions of oxidative stress and at the actions of the liposomal drug “Butaselmevit”. The research was carried out on young white laboratory male rats of the Vistar line with a body weight of 180-200 g, which were kept in the standard conditions of the institute vivarium of the State Scientific Research Control Institute of Veterinary Preparations and Feed Additives. Animals were divided into three groups of 20 animals in each: 1st group (K) intact animals; 2nd group (D1) – rats, affected with tetrachloromethane; group 3 (D2) – rats, affected with tetrachloromethane and treated with Botselmevit liposomal preparation. Toxic lesion of rats was caused by intramuscular administration of 50% tetrachloromethane at a dose of 0.25 ml per 100 g of animal body weight for the first and third day of the study. Animals of the experimental group D2 on the first and third day of the study, an hour after the introduction of tetrachloroethane, additionally administered a liposomal preparation at a dose of 2 ml per 1 kg of body weight of the animal. The composition of this preparation includes the following substances: butafosfan, selenium, methionine, thistle injection and vitamins A, E and D3. The development of oxidative stress in rats caused by intramuscular administration of tetrachloromethane was accompanied by suppression of protein synthesis of the liver, as evidenced by the low level of total protein and the decrease in the albumin-globulin factor. Low levels of albumin and high levels of globulins in the blood of diseased rats indicate an albumin-globulin disproportion. The indicators of liver function were quite high, namely: the level of creatinine increased by 46%, urea by 74% and total bilirubin by 34%. When applying the liposomal drug "Butaselmevit" to rats, under conditions of oxidative stress during research, the normalization of biochemical parameters occurs in the blood. It has been proven that modeling of the stress response in rats of the experimental group leads to a probable decrease in the level of reduced glutathione and the activity of glutathione peroxidase in the second and fifth days of the experiment. When applying the liposomal drug Butaselmevit to rats, under conditions of oxidative stress during the studies, activation of the glutathione linkage of the antioxidant system occurs in the blood, indicating an increase in the level of reduced glutathione and the activity of glutathione peroxidase in the blood of animal data. At the 14th day of the research, the level of reduced glutathione and the activity of glutathione peroxidase in blood of the experimental group D2 were the highest. The results of the research indicate the antioxidant properties of the new liposomal drug “Butaselmevit”.