Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn’t cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.
This study looked into the synthesis and study of Dextrane Sulfate–Doxorubicin Nanoparticles (DS–Dox NP) that are sensitive to amylase and show anticoagulant properties. The particles were obtained by the method of solvent replacement. They had a size of 305 ± 58 nm, with a mass ratio of DS:Dox = 3.3:1. On heating to 37 °C, the release of Dox from the particles was equal to 24.2% of the drug contained. In the presence of amylase, this ratio had increased to 42.1%. The study of the biological activity of the particles included an assessment of the cytotoxicity and the effect on hemostasis and antitumor activity. In a study of cytotoxicity on the L929 cell culture, it was found that the synthesized particles had less toxicity, compared to free doxorubicin. However, in the presence of amylase, their cytotoxicity was higher than the traditional forms of the drug. In a study of the effect of DS–Dox NP on hemostasis, it was found that the particles had a heparin-like anticoagulant effect. Antitumor activity was studied on the model of ascitic Zaidel hepatoma in rats. The frequency of complete cure in animals treated with the DS–Dox nanoparticles was higher, compared to animals receiving the traditional form of the drug.
Èññëåäîâàíî âëèÿíèå ãèïåðòîíè÷åñêîãî ðàñòâîðà õëîðèäà íàòðèÿ è ïðåïàðàòà Ãè-ïåðÕÀÅÑ íà ïîêàçàòåëè ëåòàëüíîñòè, îêñèãåíèðóþùóþ ôóíêöèþ ëåãêèõ è êèñëîò-íî-îñíîâíîå ñîñòîÿíèå ó êðûñ ïðè ñèíäðîìå îñòðîãî ïîâðåaeäåíèÿ ë¸ãêèõ / îñòðîì ðåñïèðàòîðíîì äèñòðåññ-ñèíäðîìå (ÑÎÏË/ÎÐÄÑ). ÑÎÏË/ÎÐÄÑ ìîäåëèðîâàëè ïóòåì èíòðàòðàõåàëüíîãî ââåäåíèÿ 0,1 ìë/êã àöåòîíà. AEèâîòíûå áûëè ðàçäåëåíû íà 4 ãðóï-ïû ïî 16 îñîáåé â êàaeäîé. AEèâîòíûå 1-é ãðóïïû (êîíòðîëü) ïðåïàðàòîâ íå ïîëó÷àëè. AEèâîòíûì îïûòíûõ ãðóïï ïðîâîäèëè ñïåöèôè÷åñêóþ òåðàïèþ, êîòîðàÿ çàêëþ÷àëàñü â îäíîêðàòíîì âíóòðèâåííîì ââåäåíèè èññëåäóåìûõ ïðåïàðàòîâ ÷åðåç 1 ÷ ïîñëå èíò-ðà-òðàõåàëüíîãî ââåäåíèÿ àöåòîíà. Êðûñàì 1-é îïûòíîé ãðóïïû ââîäèëè äåêñàìåòàçîí â äîçå 6 ìã/êã, 2-é -7,5 % ðàñòâîð õëîðèäà íàòðèÿ â îáú¸ìå 4 ìë/êã, 3-é -6 % ðàñòâîð ãèäðîêñèýòèëêðàõìàëà â ñî÷åòàíèè ñ 7,2 % ðàñòâîðîì õëîðèäà íàòðèÿ (ÃèïåðÕÀÅÑ) â äîçå 4 ìë/êã. Äëÿ îöåíêè ýôôåêòèâíîñòè èçó÷àåìûõ ìåòîäîâ òåðàïèè îïðåäåëÿëè ÷àñ-òîòó äûõàíèÿ, ïîêàçàòåëè êèñëîðîäíîãî ñòàòóñà è êèñëîòíî-îñíîâíîãî ñîñòîÿíèÿ, à òàêaeå ôèêñèðîâàëè ëåòàëüíîñòü íà ïðîòÿaeåíèè 6 ñóò îò ìîìåíòà ìîäåëèðîâàíèÿ ÑÎÏË/ÎÐÄÑ. Óñòàíîâëåíî, ÷òî âñå ïðèìåíÿåìûå ñõåìû óëó÷øàþò ðåçóëüòàòû ëå÷å-íèÿ ÑÎÏË/ÎÐÄÑ, ñíèaeàþò îáùóþ ñìåðòíîñòü è ñìåðòíîñòü íà ðàííèõ ýòàïàõ ëå÷å-íèÿ.  ïåðâûå ÷àñû ïîñëå àñïèðàöèè àöåòîíà îíè ïðåäîòâðàùàþò ðàçâèòèå òîêñè÷åñ-êîãî îòåêà ëåãêèõ è óìåíüøàþò âûðàaeåííîñòü ãèïîâåíòèëÿöèè, íà áîëåå ïîçäíèõ ýòà-ïàõ -óìåíüøàþò âûðàaeåííîñòü äèôôóçèîííûõ íàðóøåíèé. Äîñòîâåðíûõ ðàçëè÷èé ïî âëèÿíèþ íà ëåòàëüíîñòü è ïîêàçàòåëè îêñèãåíàöèè ìåaeäó ïðèìåíÿåìûìè ñõåìàìè òåðàïèè íå âûÿâëåíî.Êëþ÷åâûå ñëîâà: îñòðûé ðåñïèðàòîðíûé äèñòðåññ-ñèíäðîì; ãèïåðòîíè÷åñêèé ðàñ-òâîð õëîðèäà íàòðèÿ; ãèäðîêñèýòèëêðàõìàë; äåêñàìåòàçîí; îêñèãåíàöèÿ; êðûñû. ÂÂÅÄÅÍÈÅÑèíäðîì îñòðîãî ïîâðåaeäåíèÿ ë¸ãêèõ (ÑÎÏË) è åãî íàèáîëåå òÿaeåëàÿ ôîðìà -îñòðûé ðåñïèðàòîðíûé äèñòðåññ-ñèíäðîì (ÎÐÄÑ) -ÿâëÿþòñÿ íåñïåöèôè÷å-ñêîé ðåàêöèåé íà ñèñòåìíîå âîñïàëåíèå èëè òÿaeåëîå òðàâìàòè÷åñêîå ïîâðåaeäåíèå è ñîïðîâîaeäàþòñÿ âûñî-êîé ëåòàëüíîñòüþ. Íåñìîòðÿ íà èíòåíñèâíûå èññëåäî-âàíèÿ ïàòîãåíåçà è ðàçðàáîòêó ìåòîäîâ òåðàïèè ÑÎÏË/ÎÐÄÑ, çà ïîñëåäíèå 20 ëåò íå îòìå÷åíî çàìåò-íîãî êëèíè÷åñêîãî óñïåõà [5,13].  íàñòîÿùåå âðåìÿ ìîaeíî âûäåëèòü 2 îñíîâíûõ íàïðàâëåíèÿ ðàçâèòèÿ èíòåíñèâíîé òåðàïèè ÑÎÏË/ÎÐÄÑ: âî-ïåðâûõ, ðàçðà-áîòêó ìåòîäîâ âñïîìîãàòåëüíîé è èñêóññòâåííîé âåí-òèëÿöèè ëåãêèõ è, âî-âòîðûõ, -ïîèñê ïóòåé ôàðìàêî-ëîãè÷åñêîé êîððåêöèè ïàòîëîãè÷åñêèõ èçìåíåíèé â ëåãî÷íîé òêàíè. È åñëè íà ïåðâîì íàïðàâëåíèè èìå-þòñÿ îïðåäåëåííûå óñïåõè è äîñòèãíóò êîíñåíñóñ â âûáîðå ñòðàòåãèè è òàêòèêè ðåñïèðàòîðíîé ïîääåðae-êè [1,14], òî ôàðìàêîòåðàïèÿ ÎÐÄÑ îñòàåòñÿ ïðåäìå-òîì äèñêóññèé [5,10,13]. Òàê, ýêçîãåííûé ñóðôàêòàíò, îêñèä àçîòà, ïðîñòàãëàíäèí E 1 , êåòîêîíàçîë, N-àöåòèë-öèñòåèí è àêòèâèðîâàííûé ïðîòåèí C íå ïîêàçàëè ýô-ôåêòèâíîñòè â ëå÷åíèè ÑÎÏË/ÎÐÄÑ, è èõ èññëåäîâà-íèÿ áûëè äîñðî÷íî ïðåêðàùåíû [5,10]. Ñåãîäíÿ äëÿ ëå÷åíèÿ ÑÎÏË/ÎÐÄÑ íàèáîëåå øèðîêî èñïîëüçóþòñÿ ãëþêîêîðòèêîñòåðîèäû [1,8,11]. Êðîìå òîãî, îáÿçà-òåëüíûì êîìïîíåíòîì èíòåíñèâíîé òåðàïèè ÿâëÿþòñÿ èíôóçèîííûå ñðåäû. Ðîëü è ìåñòî êàaeä...
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