Thrombolytic therapy by high doses of streptokinase (SK) that are stipulated by its rapid clearance is accompanied by side effects. In this work for the purpose of lifetime prolongation in bloodstream and decrease in side effects SK was included in microcapsules from water-soluble polyethyleneglygol (PEG) using the double emulsification method. By variation of the emulsification conditions, molecular weight of PEG (20 or 40 kDa) and PEG/SK ratio (12 or 8 mg PEG/1000 IU SK) it was obtained four preparations of PEG-microcapsules with high percent of SK inclusion (approximately 90-91%), which has completely preserved its fibrinolytic activity and released from microcapsules with different rates. The time of SK full release from obtained PEG-microcapsules was varied from 45 to 90 min (pH 7.4; 37 degrees C). The comparative in vitro study ofthrombolytic and side effects of free SK and SK*PEG-microcapsules was conducted. It was found that at equal doses (500 IU/mL) the lysis rates of human plasma clots under the action of encapsulated preparations of SK (with the exception of a small lag period) were equal to the lysis rate induced by free SK. Besides, SK*PEG-microcapsules caused a less exhaustion of plasminogen and fibrinogen in plasma than free SK.

Thrombolytic therapy with high doses of streptokinase (SK), which are required due to its rapid clearance from the bloodstream, is accompanied by side effects. In this work, the SK was incorporated into water-soluble polyethylene glycol (PEG) microcapsules with the double emulsification method in order to increase its lifetime in bloodstream and decrease side effects. Four preparations of SK*PEG-microcapsules with a high degree of the SK enclosure (∼90–91%) and total retention of fibrinolytic activity were produced under varying emulsification conditions (PEG molecular mass 20 or 40 kDa and PEG/SK ratio 12 or 8 mg of PEG/1000 IU SK). SK was released from the PEG-microcapsules at different rates: the time of complete release varied from 45 to 90 min (pH 7.4, 37°C). Comparative in vitro study of thrombolytic activity and side effects of the SK in a free and encapsulated state was conducted. It was found that the rate of human plasma clot lysis under the action of encapsulated SK preparations is equal (with exception of a short lag-period) to the rate of lysis induced by the free SK, provided that the doses were equal (500 IU/mL). Furthermore, the SK*PEG-microcapsules caused the reduced exhaustion of plasminogen and fibrinogen in plasma when compared with the free SK.

Тромболитическая терапия высокими дозами стрептокиназы (СК), необходимость которых обусловлена быстрым клиренсом ее из кровотока, сопровождается побочными эффектами. В данной работе для увеличения времени жизни в кровотоке и снижения побочных эффектов СК была включена в микрокапсулы из водорастворимого полиэтиленгликоля (ПЭГ) методом двойного эмульгирования. Вариацией условий эмульгирования (молекулярная масса ПЭГ 20 или 40 кДа и соотношение ПЭГ/СК 12 или 8 мг ПЭГ/1000 МЕ СК), получены четыре препарата СК*ПЭГ-микрокапсул с высокой степенью включения СК ( 90 91) и полным сохранением еe фибринолитической активности. СК высвобождалась из полученных ПЭГ-микрокапсул с разными скоростями: время полного ее высвобождения варьировалось от 45 до 90 мин (рН 7.4, 37°С). Проведено сравнительное in vitro-изучение тромболитических и побочных эффектов СК в свободном и микрокапсулированном состояниях. Найдено, что при равных дозах (500 МЕ/мл) скорости лизиса сгустков из плазмы крови человека под действием капсулированных препаратов СК (за исключением небольшого лаг-периода) равны скорости лизиса, индуцированной свободной СК. При этом СК*ПЭГ-микрокапсулы вызывали меньшее истощение плазминогена и фибриногена в плазме, чем свободная СК.