The specific activity of drug formulation of doxorubicin embedded into phospholipid nanoparticles with diameter less than 30 nm ("Doxolip") was studied in mice LLC carcinoma. Doxolip was prepared according to technology that was elaborated in Institute earlier. Doxorubicin tumor accumulation after intraperitoneal administration (at 4 h) was 4.5 times higher for Doxolip, than for free doxorubicin. The study of doxorubicin antitumor activity in developing tumor after single intravenous administration, 48 h after inoculation, showed, that: 1) tumor growth inhibition of Doxolip was observed at 6th day, while it was only at 11th day for free doxorubicin and revealed in less extent; 2) there was no antitumor effect of free doxorubicin at 8 days after administration of doses 2 and 4 mg/kg, but it was observed for Doxolip in dose-dependent manner, 10% and 30% correspondently. In experiment with developed tumor weekly Doxolip intraperitoneal administration (5 mg/kg, 3 weeks beginning from 7 days after inoculation) resulted in 56% decrease of tumor volume as compared with control. This parameter for free doxorubicin was 2.8 times lower. The obtained data indicate, that incorporation of doxorubicin into phospholipid nanoparticles with size up to 30 nm as delivery system increases its tumor accumulation and results to increase of specific activity both in intraperitoneal and in intravenous administration.
Na modeli opukholi u mysheĭ s kartsinomoĭ LLC issledovano spetsificheskoe deĭstvie lekarstvennoĭ kompozitsii na osnove doksorubitsina, vkliuchennogo v fosfolipidnye nanochastitsy razmerom do 30 nm (Doksolip), poluchennoĭ po razrabotannoĭ v IBMKh tekhnologii. Pri vnutribriushinnom vvedenii Doksolipa nakoplenie doksorubitsina v opukholi bylo v 4,5 raza bol'she, chem dlia svobodnogo doksorubitsina. Issledovanie éffektivnosti doksorubitsina na razvivaiushcheĭsia opukholi posle odnokratnogo vnutrivennogo vvedeniia cherez 48 ch posle inokuliatsii opukholi pokazalo, chto 1) tormozhenie rosta opukholi dlia Doksolipa nabliudaetsia na 6-e sutki, a dlia svobodnogo doksorubitsina na 11-e sutki, prichem v znachitel'no men'sheĭ stepeni; 2) protivoopukholevyĭ éffekt na 8-e sutki pri dozakh 2 i 4 mg/kg dlia svobodnogo doksorubitsina ne proiavlialsia, a dlia Doksolipa imel dozozavisimyĭ kharakter, sostavliaia, sootvetstvenno, 10% i 30%. Na razvivsheĭsia opukholi pri vnutribriushinnom ezhenedel'nom (v techenie 3-kh nedel', nachinaia s 7-i sutok posle inokuliatsii) vvedenii (5 mg/kg) Doksolip snizhal ob"em opukholi na 56% v sravnenii s kontrolem (bez lecheniia). Dlia svobodnogo doksorubitsina étot pokazatel' byl v 2,8 raza nizhe. Poluchennye dannye svidetel'stvuiut o tom, chto vkliuchenie doksorubitsina v fosfolipidnye nanochastitsy razmerom do 30 nm kak sistemu transporta sposobstvuet znachitel'nomu uvelicheniiu ego nakopleniia v opukholi i privodit k uvelicheniiu spetsificheskoĭ aktivnosti kak pri vnutribriushinnom, tak i pri vnutrivennom vvedenii.
Keywords: doxorubicin; growth inhibition; mice LLC carcinoma; phospholipids nanoparticles; tumor accumulation.