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


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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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作者简介

T. 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. Osipova

D. Mendeleev University of Chemical Technology of Russia

Research Scientist

A. Belov

D. Mendeleev University of Chemical Technology of Russia

Ph.D. (Chem.), Research Scientist

O. Maksimenko

D. Mendeleev University of Chemical Technology of Russia

Ph.D. (Chem.), Research Scientist

V. Balabanyan

M.V. Lomonosov Moscow State University

Dr.Sc. (Pharm.), Leading Research Scientist

S. Gelperina

D. Mendeleev University of Chemical Technology of Russia

Dr.Sc. (Chem.), Professor

参考

  1. Wacker M. Nanocarriers for intravenous injection - the long hard road to the market. Int. J. Pharm. 2013; 457(1):50-62.
  2. Gelperina S., Maksimenko O., Khalansky A.S., Vanchugova L., Shipulo E. et al. Drug delivery to the brain using surfactant coated poly (lactide-co-glycolide) nanoparticles: influence of the formulation parameters. Eur. J. Pharm. Biopharm. 2010: 74(2):157-163.
  3. Pereverzeva E., Treschalin I.D., Treschalin M.I., Arantseva D. et al. Toxicological study of doxorubicin-loaded PLGA nanoparticles for the treatment of glioblastoma. Int. J. Pharm. 2019; 554:161-178.
  4. Maksimenko O., Malinovskaya Ju., Shipulo E., Osipova N., Razzhivina V. et al. Doxorubicin-loaded PLGA nanoparticles for the chemotherapy of glioblastoma: Towards the pharmaceutical development. Int. J. Pharm. 2019; 572: 118733.
  5. Kumskova N., Ermolenko Yu., Osipova N., Semyonkin A., Kildeeva N. et al. How subtle differences in polymer molecular weight affect doxorubicin-loaded PLGA nanoparticles degradation and drug release. J. Microencapsul. 2020; 37(3):283-295.
  6. Yu S., Li Sh., Yang H., Lee F., Wu J. T., Qian M.G.et al. A novel liquid chromatography/tandem mass spectrometry based depletion method for measuring red blood cell partitioning of pharmaceutical compounds in drug discovery. Rapid Commun. Mass. Spectrom. 2005; 19(2):250-254.
  7. Tewes F., Munnier E., Antoonet B., Okassa L.N., Cohen-Jonathan S. et al. Comparative study of doxorubicin-loaded poly (lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods. Eur. J. Pharm. Biopharm. 2007; 66(3):488-492.
  8. Zelepukin I.V., Yaremenko A.V., Shipunova V.O., Babenyshev A.V., Balalaeva I.V. et al. Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth. Nanoscale. 2019; 11(4):1636-1646.
  9. Kalamaridis D., DiLoreto K. Drug partition in red blood cells. Optimization in Drug Discovery. Humana Press. Totowa, NJ. 2014; р. 39-47.
  10. Terasaki T., Iga T., Sugiyama M., Hanano M. Pharmacokinetic study on the mechanism of tissue distribution of doxorubicin: interorgan and interspecies variation of tissue-to-plasma partition coefficients in rats, rabbits, and guinea pigs. J. Pharm. Sci. 1984; 73(10):1359-1363.
  11. Colombo T., Broggini M., Garattini S., Donelli M.G. Diferential a driamycin® distribution to blood components. Eur. J. Drug Metab. Pharmacokinet. 1981;6(2):115-122.

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