Некоторые аспекты получения липосомальной формы оксалиплатина
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Дата
2015
ORCID
DOI
Науковий ступінь
Рівень дисертації
Шифр та назва спеціальності
Рада захисту
Установа захисту
Науковий керівник
Члени комітету
Видавець
Московский государственный университет тонких химических технологий им. М. В. Ломоносова
Анотація
Работа посвящена обзору лабораторных методов получения липосом с оксалиплатином и их эффективности в экспериментах in vivo и in vitro. Проведен анализ существующих методов получения и дана оценка их применимости в фармацевтической промышленности для производства липосомальной формы оксалиплатина.
Methods for creations of oxaliplatin liposomal form in laboratory scale are discussed in this mini-review. Analysis of existed methods has been carried out, and the estimation of their usage in pharmaceutical industry view has been given. Oxaliplatin is one of the modern anticancer medicines, which is used both in monotherapy and in combination with other anticancer agents. One of the disadvantages of oxaliplatin as an anticancer drug is high neuro- and cardiotoxicity, which can be reduced by the creation of its liposomal form. In most methods, PEG-conjugated lipids were used as a part of phospholipids’ bilayer. Cationic liposomes modified with DSPE (distearoyl phosphatidyl ethanolamine)-PEG₂₀₀₀, with composition PC (phosphatidyl choline)/Chol (cholesterol)/DSPE-PEG₂₀₀₀ (2/1/0.2 molar ratio) showed in vivo higher efficiency against human carcinoma SW480 line on mice both in comparison with a control group and with a free oxaliplatin treated group. Moreover, the absence of cachexia, in case of liposomal oxaliplatin was noted. Also, the influence of Chol on liposomes stability was studied. It was discovered that addition of 40 % mol of Chol to liposomes with HSPC (hydrogenated soybean PC)/DSPC-PEG₂₀₀₀ increased encapsulation by 8 % within 24 h at 37 °C. Comparison of trehalose and L-arginine for liposomes HSPC/Chol/PEG₂₀₀₀ was carried out. Both cryoprotectors showed appropriate stability results in a ratio of 1 : 4 to lipids. As a conclusion, liposomal oxaliplatin is a prospective medicine with less toxicity and higher efficiency against tumors in comparison with a free oxaliplatin.
Methods for creations of oxaliplatin liposomal form in laboratory scale are discussed in this mini-review. Analysis of existed methods has been carried out, and the estimation of their usage in pharmaceutical industry view has been given. Oxaliplatin is one of the modern anticancer medicines, which is used both in monotherapy and in combination with other anticancer agents. One of the disadvantages of oxaliplatin as an anticancer drug is high neuro- and cardiotoxicity, which can be reduced by the creation of its liposomal form. In most methods, PEG-conjugated lipids were used as a part of phospholipids’ bilayer. Cationic liposomes modified with DSPE (distearoyl phosphatidyl ethanolamine)-PEG₂₀₀₀, with composition PC (phosphatidyl choline)/Chol (cholesterol)/DSPE-PEG₂₀₀₀ (2/1/0.2 molar ratio) showed in vivo higher efficiency against human carcinoma SW480 line on mice both in comparison with a control group and with a free oxaliplatin treated group. Moreover, the absence of cachexia, in case of liposomal oxaliplatin was noted. Also, the influence of Chol on liposomes stability was studied. It was discovered that addition of 40 % mol of Chol to liposomes with HSPC (hydrogenated soybean PC)/DSPC-PEG₂₀₀₀ increased encapsulation by 8 % within 24 h at 37 °C. Comparison of trehalose and L-arginine for liposomes HSPC/Chol/PEG₂₀₀₀ was carried out. Both cryoprotectors showed appropriate stability results in a ratio of 1 : 4 to lipids. As a conclusion, liposomal oxaliplatin is a prospective medicine with less toxicity and higher efficiency against tumors in comparison with a free oxaliplatin.
Опис
Ключові слова
фосфолипиды, субстанции лекарственные, промышленность фармацевтическая, phospholipids, drug substances, liposomal preparations, pharmaceutical industry
Бібліографічний опис
Стадниченко А. В. Некоторые аспекты получения липосомальной формы оксалиплатина / А. В. Стадниченко, Ю. М. Краснопольский, В. И. Швец // Тонкие химические технологии = Fine Chemical Technologies. – 2015. – Т. 10, № 1. – С. 60-65.