CYTOTOXICITY AND HEMOCOMPATIBILITY OF DOXORUBICIN-LOADED PLGA NANOPARTICLES-Reference-Cited by-同舟云学术

CYTOTOXICITY AND HEMOCOMPATIBILITY OF DOXORUBICIN-LOADED PLGA NANOPARTICLES

Published:2020-03-22 Issue:1 Volume:19 Page:71-80
ISSN:1726-9792
Container-title:Russian Journal of Biotherapy
language:
Short-container-title:Rossijskij bioterapevtičeskij žurnal

Author:

Malinovskaya Yu. A.¹^ORCID,Kovalenko E. I.²^ORCID,Kovshova T. S.¹^ORCID,Osipova N. S.³^ORCID,Maksimenko O. O.³^ORCID,Balabanyan V. Yu.⁴^ORCID,Razzhivina V. A.⁵,Grechikhina M. V.²,Boiko A. A.²^ORCID,Gelperina S. E.³^ORCID

Affiliation:

1. Drug Technology LLC; M. V. Lomonosov Moscow State University; D. Mendeleev University of Chemical Technology of Russia

2. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

3. Drug Technology LLC; D. Mendeleev University of Chemical Technology of Russia

4. M. V. Lomonosov Moscow State University

5. Drug Technology LLC

Abstract

Introduction. The use of polymeric biodegradable nanoparticles (NP) as drug delivery systems is a promising approach to overcome histohematomatic barriers. Thus, poloxamer 188-coated poly (lactide-co-glycolide) (PLGA) NP are able to overcome blood-brain barrier and to deliver therapeutic agents, in particular doxorubicin, into intracranial tumour upon intravenous administration. It is important to evaluate NP interaction with blood components in preclinical studies.The objective of the study was to investigate cytotoxicity and hemocompatibility of doxorubicin-loaded PLGA NP (Dox-PLGA NP), to essess NP uptake by glioblastoma cells.Materials and methods. The influence of NP on coagulation cascade was evaluated by prothrombin time measuring before and after plasma incubation with NP. To assess NP thrombogenicity the platelet activation level was determined by flow cytometry. The NP hemolytic activity (released hemoglobin concentration) was measured spectrophotometrically. NP cytotoxicity was determined by MTS assay. NP uptake by human glioblastoma cells was evaluated by flow cytometry.Results. Dox-PLGA NP did not influence blood coagulation time and thrombocyte activity at concentrations up to 100 mcg/mL: PT values were 12–15 s for all tested samples, and P-selectin expression level did not exceed 15 %. All samples were not hemolytic after 3 h of incubation. Cytotoxicity of doxorubicin released from PLGA NP on glioma U87MG cells was comparable to that of free doxorubicin. As shown by flow cytometry Dox-PLGA NP were efficiently internalized into the cells.Conclusion. The study of hemocompatibility confirmed the safety of Dox-PLGA NP: NP did not influence blood coagulation system and did not induce hemolysis. NP were efficiently internalized into the human glioblastoma cells and produced considerable antitumor effect in vitro.

Publisher

Publishing House ABV Press

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