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Номер №3, 2022 - стр. 28-34

Влияние простатических пептидов на трансмембранный перенос ломефлоксацина DOI: 10.29188/2222-8543-2022-15-3-28-34

Для цитирования: Духанин А.C. Влияние простатических пептидов на трансмембранный перенос ломефлоксацина. Экспериментальная и клиническая урология 2022;15(3)28-34; https://doi.org/10.29188/2222-8543-2022-15-3-28-34
Duhanin A.S.
Сведения об авторах:
  • Духанин А.С. – д.м.н., профессор, ведущий научный сотрудник лаборатории молекулярной фармакологии ФГАОУ ВО «РНИМУ им. Н.И. Пирогова»; Москва, Россия; РИНЦ AuthorID 91676
720

Введение. Применение пептидов, проникающих в клетку без участия мембранных белков и способных осуществлять внутриклеточный транспорт связанных с ними низкомолекулярных веществ, открывает новый этап в разработке целенаправленной доставки лекарственных веществ к терапевтическим мишеням.

Цель. Оценка влияния простатических пептидов препарата Витапрост® (экстракт предстательной железы) на трансмембранный транспорт антимикробного препарата ломефлоксацин.

Материалы и методы. В первой серии изучены эффекты простатических пептидов на способность ломефлоксацина проходить через искусственные мембраны путем пассивной диффузии (метод PAMPA -parallel artificial membrane permeability assay). Во второй серии изучены эффекты простатических пептидов на клеточную проницаемость ломефлоксацина в модели Сасо-2.

Результаты. Сравнительное исследование эффективной проницаемости мембраны (logPe) для ломефлоксацина в отсутствии (контрольная группа) и присутствии простатических пептидов (экстракт предстательной железы в концентрации 10 мг/мл) показало, что сочетанное применение ломефлоксацина и простатических пептидов приводит к достоверному повышению величины logPe, прирост составляет в среднем 29%. Специфический характер выявленного взаимодействия был подтвержден: добавление бета-меркаптоэтанола (BME) в донорный отсек не влияло на проницаемость чистого ломефлоксацина, но подавляло карго-эффект простатических пептидов. Рассчитанный на модели Caco-2 коэффициент проницаемости (Papp) для ломефлоксацина в комплексе с пептидами составил 13,04±1,80×10-6 см/с, в то время как для ломефлоксацина – 10,31±0,76×10-6 см/с.

Заключение. Сопоставление полученных данных двух серий экспериментов свидетельствует о наличии прямого карго-эффекта простатических пептидов на трансмембранный транспорт ломефлоксацина в условиях in vitro.

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ломефлоксацин; простатические пептиды; эффективная проницаемость мембраны; Caco-2; карго-эффект

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