Calcium phosphate and composite materials functionalization of bioactive agents for its target delivery to the bone

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Abstract


Aim of the study. The development of the method of octacalcium phosphate (OCP) and mineral-polymer composite material functionalization with biological agents (human platelet lysate (PL) growth factors and antibiotic vancomycin) by the biomimetic coprecipitation principle technique.

Materials and methods. The OCP and the mineral-polymer composite matrices (sodium alginate / gelatin / OCP) functionalization was obtained by biomimetic coprecipitation of calcium phosphates and the bioactive molecules on their surface. The materials structure was examined by electron microscopy. The functionalization efficiency was determined by measurement of the incorporated compounds in solution, as well as by analysis of their release over the 8 days. The antimicrobial activity of vancomycin functionalized samples was evaluated by in vitro disk diffusion method against the Staphylococcus aureus strain.

Results. The evaluation of incorporated molecules release showed that the OCP functionalization with vancomycin is more effective than PL. The antibiotic release had continued for three days, while PL growth factors — only for 30 minutes. The incorporated into a composite matrix vancomycin was completely released within 24 h. In vitro study of the functionalized composite samples showed growth delay of the Staphylococcus aureus strain in dependence on antibiotic content.

Conclusion. The developed method of drug incorporation during biomimetic precipitation allowed to create target delivery system which transfer antibiotic to the bone defect.


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About the authors

Ekaterina A. Kuvshinova

P.A.Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre of the Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: beliay@mail.ru
ORCID iD: 0000-0003-4331-239X
SPIN-code: 5228-5640
Scopus Author ID: 56736479200

Russian Federation, 2-nd Botkinskiy str, 3, Moscow, 125284

junior researcher

Natalia V. Petrakova

Institutution of Russian Academy of Science A.A. Baikov Institute of Metallurgy and Material Science

Email: petrakova.nv@mail.ru

Russian Federation, Leninskiy str. 49, Moscow, 119334

candidate of sciences, researcher

Natalya S. Sergeeva

P.A.Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre of the Ministry of Healthcare of the Russian Federation

Email: prognoz.06@mail.ru

Russian Federation, 2-nd Botkinskiy str, 3, Moscow, 125284

doctor of biological sciences, professor, head of the department

Irina K. Sviridova

P.A.Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre of the Ministry of Healthcare of the Russian Federation

Email: prognoz.06@mail.ru

Russian Federation, 2-nd Botkinskiy str, 3, Moscow, 125284

candidate of biological sciences, leading researcher

Valentina A. Kirsanova

P.A.Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre of the Ministry of Healthcare of the Russian Federation

Email: prognoz.06@mail.ru

Russian Federation, 2-nd Botkinskiy str, 3, Moscow, 125284

candidate of biological sciences, researcher

Suraya A. Ahmedova

P.A.Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre of the Ministry of Healthcare of the Russian Federation

Email: prognoz.06@mail.ru

Russian Federation, 2-nd Botkinskiy str, 3, Moscow, 125284

candidate of biological sciences, researcher

Pavel A. Karalkin

P.A.Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological Centre of the Ministry of Healthcare of the Russian Federation

Email: pkaralkin@gmail.com

Russian Federation, 2-nd Botkinskiy str, 3, Moscow, 125284

candidate of biological sciences, senior researcher

Anastasia Y. Teterina

Institutution of Russian Academy of Science A.A. Baikov Institute of Metallurgy and Material Science

Email: kinskusha@mail.ru

Russian Federation, Leninskiy str. 49, Moscow, 119334

candidate of technical sciences, junior researcher

Vladimir S. Komlev

Institutution of Russian Academy of Science A.A. Baikov Institute of Metallurgy and Material Science

Email: komlev@mail.ru

Russian Federation, Leninskiy str. 49, Moscow, 119334

PhD, corresponding member of the Russian Academy of Sciences, director

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Supplementary files

Supplementary Files Action
1.
Fig. 1. The release dynamic of platelet lysate protein from octacalcium phosphate upon incorporation in 10% (curve 1) and 20% (curve 2) platelet lysate solution

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2.
Fig. 2. The release dynamic of vancomycin from octacalcium phosphate upon incorporation in solutions with antibiotic concentration 8.0 mg/ml (curve 1) and 16.0 mg/ml (curve 2)

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3.
Fig. 3. SEM-photographs of the initial composite material: a — ×250, b — ×5000; a modified composite material: c — ×5000

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4.
Fig. 4. The release dynamic of vancomycin from composite matrix upon incorporation in solutions with antibiotic concentration 5.0 mg / ml (curve 1) and 50.0 mg / ml (curve 2)

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5.
Fig. 5. Zones for suppressing bacterial growth: a — control samples (non-functionalized matrices), 0–5 mm; b — functionalized samples containing 0.1 mg/mg vancomycin, 16.0 mm; c — functionalized samples containing 2.0 mg/ml vancomycin, 20.0 mm

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Copyright (c) 2020 Kuvshinova E.A., Petrakova N.V., Sergeeva N.S., Sviridova I.K., Kirsanova V.A., Ahmedova S.A., Karalkin P.A., Teterina A.Y., Komlev V.S.

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