Onkopediatria, volume 3, issue 3, pages 188-199

Сравнительные исследования противоопухолевой активности и безопасности нового препарата белково-векторной доставки актиномицинового ряда на экспериментальных опухолевых моделях у мышей

Kruglyi B.I., Nikolskaya E.D., Severin E.S., Barsegyan G.G., Yabbarov N.G., Tereshchenko O.G., Zhunina O.A., Zenin V.A., Tyulyaev A.I.
Publication type: Journal Article
Publication date: 2016-01-01
Journal: Onkopediatria
Quartile SCImago
Q4
Quartile WOS
—
Impact factor: —
ISSN: 23119977
Oncology
Pediatrics, Perinatology and Child Health
Abstract
Introduction. The possible acute toxicity and antitumor activity of the novel protein-targeted delivery drug — “Afotid” — was investigated. The active cytostatic agent is dactinomycin incorporated into biodegradable polylactide (PLGA) nanoparticles with AFP as a protein carrier. Objective. To study and compare drug toxicity and   anti-neoplastic activity in solid and liquid tumor models in mice. Materials and Methods. Ehrlich ascites carcinoma (EAC) model was developed in 90 outbred female mice, and Lymphocytic leukemia P388 solid tumor model – in 140 female DBA/2 mice. The toxicometry with survival rate of mice was estimated by escalation the dosing according to J.Т. Litchfield and F. Wilcoxon method. The antitumor activity was estimated by the indexes of tumor growth inhibition (TGI) and average lifespan (ALS). Results. The targeted drug delivery is significantly less toxic than the prototype. The phenomenon of substantial decrease of toxic effects in mice with tumor model equalized to healthy animals was detected. LD50 increased up to 1.580 mg/kg for dactinomycin vs 0.601 mg/kg for prototype in healthy mice. This is critically upscale potentialities for clinical use of protein-targeted drug delivery of “Aftotid” in therapy with higher single and course doses which results in the significant increase of antitumor activity and decrease of toxic side effects. 7-Aminoactinomycin D (7-AAD) conjugated with AFP in nanoparticles shows substantially higher cumulation (4.6 fold P<0.0001) in tumor cells after intraperitoneal injection to EAC mice compared to prototype compound. The antitumor effect of protein-targeted delivery drug in comparison with prototype is significantly higher. The effect based on TGI criteria for “Afotid” is 1.48 fold higher in dactinomycin-vulnerable lymphocytic leukemia P388 model and 2.32 fold higher for dactinomycin-resistant lymphocytic leukemia P388 model. According to ALS criteria, the increasing rates are 2.71 fold and 3.525 fold higher respectively. Conclusion. The novel protein-targeted delivery compound has significantly higher antitumor activity and lower toxicity as compared with the prototype.
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Kruglyi B.I. et al. Сравнительные исследования противоопухолевой активности и безопасности нового препарата белково-векторной доставки актиномицинового ряда на экспериментальных опухолевых моделях у мышей // Onkopediatria. 2016. Vol. 3. No. 3. pp. 188-199.
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Kruglyi B.I., Nikolskaya E.D., Severin E.S., Barsegyan G.G., Yabbarov N.G., Tereshchenko O.G., Zhunina O.A., Zenin V.A., Tyulyaev A.I. Сравнительные исследования противоопухолевой активности и безопасности нового препарата белково-векторной доставки актиномицинового ряда на экспериментальных опухолевых моделях у мышей // Onkopediatria. 2016. Vol. 3. No. 3. pp. 188-199.
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TY - JOUR
DO - 10.15690/onco.v3i3.1597
UR - https://doi.org/10.15690%2Fonco.v3i3.1597
TI - Сравнительные исследования противоопухолевой активности и безопасности нового препарата белково-векторной доставки актиномицинового ряда на экспериментальных опухолевых моделях у мышей
T2 - Onkopediatria
AU - Kruglyi, B I
AU - Nikolskaya, E D
AU - Severin, E S
AU - Barsegyan, G G
AU - Yabbarov, N G
AU - Tereshchenko, O G
AU - Zhunina, O A
AU - Zenin, V A
AU - Tyulyaev, A I
PY - 2016
DA - 2016/01/01 00:00:00
PB - Paediatrician Publishers LLC
SP - 188-199
IS - 3
VL - 3
SN - 2311-9977
ER -
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@article{2016,
author = {B I Kruglyi and E D Nikolskaya and E S Severin and G G Barsegyan and N G Yabbarov and O G Tereshchenko and O A Zhunina and V A Zenin and A I Tyulyaev},
title = {Сравнительные исследования противоопухолевой активности и безопасности нового препарата белково-векторной доставки актиномицинового ряда на экспериментальных опухолевых моделях у мышей},
journal = {Onkopediatria},
year = {2016},
volume = {3},
publisher = {Paediatrician Publishers LLC},
month = {jan},
url = {https://doi.org/10.15690%2Fonco.v3i3.1597},
number = {3},
pages = {188--199},
doi = {10.15690/onco.v3i3.1597}
}
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