Open AccessCYTOTOXICITY AND HEMOCOMPATIBILITY OF DOXORUBICIN-LOADED PLGA NANOPARTICLES
Author(s) -
Ю. В. Малиновская,
Elena I. Kovalenko,
Tatyana Kovshova,
Nadezhda Osipova,
Olga Maksimenko,
В. Ю. Балабаньян,
V.A. Razzhivina,
М. В. Гречихина,
А. А. Бойко,
Svetlana Gelperina
Publication year - 2020
Publication title -
rossijskij bioterapevtičeskij žurnal
Language(s) - English
Resource type - Journals
eISSN - 1726-9792
pISSN - 1726-9784
DOI - 10.17650/1726-9784-2019-19-1-71-80
Subject(s) - doxorubicin , plga , cytotoxicity , flow cytometry , pharmacology , chemistry , platelet , thrombogenicity , in vitro , immunology , medicine , biochemistry , chemotherapy , surgery
. 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.