Effect of the parameters regulation of the nanoparticulate form of doxorubicin based on PLGA on the distribution between human blood plasma and red blood cells
- Authors: Kovshova T.S1,2, Osipova N.S2, Belov A.V2, Maksimenko O.O2, Balabanyan V.Y.1, Gelperina S.E2
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Affiliations:
- M.V. Lomonosov Moscow State University
- D. Mendeleev University of Chemical Technology of Russia
- Issue: Vol 23, No 8 (2020)
- Pages: 11-18
- Section: Articles
- URL: https://journals.eco-vector.com/1560-9596/article/view/112769
- DOI: https://doi.org/10.29296/25877313-2020-08-02
- ID: 112769
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Abstract
Relevance. One of the features of the pharmacokinetics of nanoparticle-based drug formulations is the different distribution of free and carrier-bound drugs (nanoparticles, liposomes) between plasma and blood cells. Aim. Evaluation of in vitro binding of doxorubicin-loaded nanoparticles (NPs) based on a copolymer of lactic and glycolic acids (PLGA) modified with poloxamer 188 (Dox-PLGA) to human red blood cells at a concentration of 10-100 μg/ml and the influence of physicochemical parameters of NPs on their binding to red blood cells. Material and methods. Dox-PLGA NPs were obtained by a "double emulsion" method. A 1% PVA solutions in phosphate buffer at pH 7.4 (Dox-PLGA/7.4) and 6.4 (Dox-PLGA/6.4) were used as the external aqueous phase. The purified Dox-PLGA/7.4(G-25) and Dox-PLGA/6.4(G-25) NPs were obtained by separation of the free fraction of doxorubicin (non-nanoparticle-bound) by gel filtration. The kinetics of doxorubicin release from NPs in vitro was determined in a 1% solution of poloxamer 188. To assess the binding of the NPs to red blood cells, the distribution coefficients KRBC/Plasma (red blood cells - plasma) and KBlood/Plasma (whole blood - plasma) were calculated after incubation in whole blood within 5, 15 and 30 minutes. The doxorubicin content in plasma was estimated by HPLC. Results. Compared to the Dox-PLGA/7.4 NPs (average size 114±1 nm), the Dox-PLGA/6.4 NPs (average size 142±2 nm) had a lower encapsulation efficiency (79.7±1.1% vs 91.0±0.7%, respectively) and a higher release rate of doxorubicin in vitro. Based on the calculated KBlood/Plasma values, the total amount of doxorubicin bound to red blood cells after 5 minutes of incubation was ~ 33% for both nanoparticulate formulations and free doxorubicin (control) over the entire concentration range. The equilibrium degree of binding (after 15 minutes of incubation) was 58-63% for free doxorubicin, 57-58% for Dox-PLGA/6.4 and 46-49% P LG A/7.4. The Dox-PLGA/6.4(G-25) NPs had the lowest equilibrium degree of binding to red blood cells (~ 34%). Conclusion. Binding of the nanoparticle-bound doxorubicin (Dox-PLGA) to human red blood cells evaluated in vitro in the concentration range of 10-100 μg/ml is lower as compared with free doxorubicin. The NPs with a higher encapsulation efficiency and loading of doxorubicin exhibit lower distribution coefficients of doxorubicin between red blood cells and blood plasma (KBlood/Plasma and KRBC/Plasma)
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About the authors
T. S Kovshova
M.V. Lomonosov Moscow State University; D. Mendeleev University of Chemical Technology of Russia
Email: kovshova.tatyana.nanofarm@gmail.com
Post-graduate Student; Research Scientist
N. S Osipova
D. Mendeleev University of Chemical Technology of RussiaResearch Scientist
A. V Belov
D. Mendeleev University of Chemical Technology of RussiaPh.D. (Chem.), Research Scientist
O. O Maksimenko
D. Mendeleev University of Chemical Technology of RussiaPh.D. (Chem.), Research Scientist
V. Yu Balabanyan
M.V. Lomonosov Moscow State UniversityDr.Sc. (Pharm.), Leading Research Scientist
S. E Gelperina
D. Mendeleev University of Chemical Technology of RussiaDr.Sc. (Chem.), Professor
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