title: [Influence of doxorubicin inclusion into phospholipid nanoparticles on tumor accumulation and specific activity].
abstract: 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.
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: N V
authors.initials: NV
authors.lastname: Medvedeva
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: T I
authors.initials: TI
authors.lastname: Torkhovskaya
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: L V
authors.initials: LV
authors.lastname: Kostryukova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: T S
authors.initials: TS
authors.lastname: Zakharova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Kudinov
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: E O
authors.initials: EO
authors.lastname: Kasatkina
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: V N
authors.initials: VN
authors.lastname: Prozorovskiy
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: O M
authors.initials: OM
authors.lastname: Ipatova
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006614:Hindlimb; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D010743:Phospholipids
keywords: doxorubicin; growth inhibition; mice LLC carcinoma; phospholipids nanoparticles; tumor accumulation