Effect of Biopolymers and Functionalized by Them Vaterite Microparticles on Platelet Aggregation

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Vaterite microparticles, metastable form of calcium carbonate, are promising forms of delivery of medicinal compounds. For more efficient delivery of target molecules (increased incorporation and retention), vaterite microparticles must be functionalized with biopolymers. In this article the effect of polysaccharides, mucin and vaterite microparticles, as well as hybrid vaterite microparticles with the above-mentioned biopolymers was studied on platelet aggregation. It was found that fucoidan, heparin and dextran sulfate (when added to platelet-rich plasma) and mucin (when added to isolated platelets) initiated cell aggregation. Pectin and chondroitin sulfate inhibited ADP- and thrombin-induced aggregation in a dose-dependent manner, mucin suppressed ADP-induced, and dextran sulfate suppressed thrombin-induced platelet aggregation. Vaterite microparticles at a concentration of 100–1000 μg/ml did not affect the aggregation of isolated platelets, but caused 10–15% cell aggregation in plasma; at the same time, at a concentration of 1000 μg/ml vaterite microparticles prevented agonist-induced cell aggregation by ~30%. It has been established that hybrid vaterite microparticles with fucoidan or heparin, when added both to platelet-rich plasma and to isolated cells, are capable to initiate platelet aggregation. Vaterite microparticles functionalized with pectin or chondroitin sulfate had no effect on spontaneous cell aggregation, and did not affect (with chondroitin sulfate) or inhibit (with pectin) agonist-induced platelet aggregation. Thus, the use of hybrid vaterite microparticles with pectin or fucoidan/heparin may be promising for the delivery of drugs aimed at modulating (inhibition with pectin or activation with fucoidan/heparin) the platelet component of hemostasis.

Full Text

Restricted Access

About the authors

D. V. Grigorieva

Belarusian State University

Author for correspondence.
Email: dargr@tut.by
Belarus, Minsk

E. V. Mikhalchik

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: dargr@tut.by
Russian Federation, Moscow

N. G. Balabushevich

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency; Lomonosov Moscow State University

Email: dargr@tut.by
Russian Federation, Moscow; Moscow

D. V. Mosievich

Lomonosov Moscow State University

Email: dargr@tut.by
Russian Federation, Moscow

М. А. Murina

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: dargr@tut.by
Russian Federation, Moscow

О. М. Panasenko

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: dargr@tut.by
Russian Federation, Moscow

А. V. Sokolov

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency; Institute of Experimental Medicine

Email: dargr@tut.by
Russian Federation, Moscow; St. Petersburg

I. V. Gorudko

Belarusian State University

Email: dargr@tut.by
Belarus, Minsk

References

  1. Trushina DB, Borodina TN, Belyakov S, Antipina MN (2022) Calcium carbonate vaterite particles for drug delivery: Advances and challenges. Mater Today Adv 14: 100214. https://doi.org/10.1016/j.mtadv.2022.100214
  2. Cavallaro G, Lazzara G, Fakhrullin R (2018) Mesoporous inorganic nanoscale particles for drug adsorption and controlled release. Ther Deliv 9: 287–301. https://doi.org/10.4155/tde-2017–0120
  3. Vikulina A, Voronin DV, Fakhrullin RF, Vinokurov VA, Volodkin D (2020) Naturally derived nano- and micro- drug delivery vehicles: halloysite, vaterite and nanocellulose. New J Chem 44: 5638–5655. https://doi.org/10.1039/C9NJ06470B
  4. Konopacka-Łyskawa D, Czaplicka N, Łapiński M, Kościelska B, Bray R (2020) Precipitation and transformation of vaterite calcium carbonate in the presence of some organic solvents. Materials (Basel) 13: 2742. https://doi.org/10.3390/ma13122742
  5. Kralj D, Brečević L, Kontrec J (1997) Vaterite growth and dissolution in aqueous solution III. Kinetics of transformation. J Cryst Growth 177: 248–257. https://doi.org/10.1016/S0022–0248(96)01128–1
  6. Svenskaya YI, Genina EA, Parakhonskiy BV, Lengert EV, Talnikova EE, Terentyuk GS, Utz SR, Gorin DA, Tuchin VV, Sukhorukov GB (2019) A simple non-invasive approach toward efficient transdermal drug delivery based on biodegradable particulate system. ACS Appl Mater Interfaces 11: 17270–17282. https://doi.org/10.1021/acsami.9b04305
  7. Svenskaya Y, Parakhonskiy B, Haase A, Atkin V, Lukyanets E, Gorin D, Antolini R (2013) Anticancer drug delivery system based on calcium carbonate particles loaded with a photosensitizer. Biophys Chem 182: 11–15. https://doi.org/10.1016/j.bpc.2013.07.006
  8. Sheng Han Y, Hadiko G, Fuji M, Takahashi M (2006) Crystallization and transformation of vaterite at controlled pH. J Cryst Growth 289: 269–274. https://doi.org/10.1016/j.jcrysgro.2005.11.011
  9. Parakhonskiy B, Tessarolo F, Haase A, Antolini R (2012) Dependence of sub-micron vaterite container release properties on pH and ionic strength of the surrounding solution. Adv Sci Technol 86: 81–85. https://doi.org/10.4028/www.scientific.net/AST.86.81
  10. Wang X, Kong R, Pan X, Xu H, Xia D, Shan H, Lu JR (2009) Role of ovalbumin in the stabilization of metastable vaterite in calcium carbonate biomineralization. J Phys Chem B113: 8975–8982. https://doi.org/10.1021/jp810281f
  11. Katsifaras A, Spanos N (1999) Effect of inorganic phosphate ions on the spontaneous precipitation of vaterite and on the transformation of vaterite to calcite. J Cryst Growth 204: 183–190. https://doi.org/10.1016/S0022–0248(99)00174–8
  12. Al Omari MM, Rashid IS, Qinna NA, Jaber AM, Badwan AA (2016) Calcium carbonate. Profiles Drug Subst Excip Relat Methodol 41: 31–132. https://doi.org/10.1016/bs.podrm.2015.11.003
  13. Choukrani G, Freile JÁ, Avtenyuk NU, Wan W, Zimmermann K, Bremer E, Dähne L (2021) High loading efficiency and controlled release of bioactive immunotherapeutic proteins using vaterite nanoparticles. Part Part Syst Charact 38: 2100012. https://doi.org/10.1002/ppsc.202100012
  14. Dong Z, Feng L, Zhu W, Sun X, Gao M, Zhao H, Chao Y, Liu Z (2016) CaCO3 nanoparticles as an ultra-sensitive tumor-pH-responsive nanoplatform enabling real-time drug release monitoring and cancer combination therapy. Biomaterials 110: 60–70. https://doi.org/10.1016/j.biomaterials.2016.09.025
  15. Mayorga IC, Astilleros JM, Fernández-Díaz L (2019) Precipitation of CaCO3 polymorphs from aqueous solutions: the role of pH and sulphate groups. Minerals 9: 1–16. https://doi.org/10.3390/min9030178
  16. Balabushevich NG, Kovalenko EA, Le-Deygen IM, Filatova LY, Volodkin D, Vikulina AS (2019) Hybrid CaCO3-mucin crystals: effective approach for loading and controlled release of cationic drugs. Mater Des 182: 108020. https://doi.org/10.1016/j.matdes.2019.108020
  17. Balabushevich NG, Lopez de Guerenu AV, Feoktistova NA, Volodkin D (2015) Protein loading into porous CaCO3 microspheres: adsorption equilibrium and bioactivity retention. Phys Chem Chem Phys 17: 2523–2530. https://doi.org/10.1039/C4CP04567
  18. Sudareva N, Suvorova O, Saprykina N, Smirnova N, Bel’tyukov P, Petunov S, Radilov A, Vilesov A (2018) Two-level delivery systems based on CaCO3 cores for oral administration of therapeutic peptides. J Microencapsul 35: 619–634. https://doi.org/10.1080/02652048.2018.1559247
  19. Shi P, Luo S, Voit B, Appelhans D, Zan X (2018) A facile and efficient strategy to encapsulate the model basic protein lysozyme into porous CaCO3. J Mater Chem B6: 4205–4215. https://doi.org/10.1039/c8tb00312b
  20. Balabushevich NG, Sholina EA, Mikhalchik EV, Filatova LY, Vikulina AS, Volodkin D (2018) Self-assembled mucin-containing microcarriers via hard templating on CaCO3 crystals. Micromachines 9: 1–16. https://doi.org/10.3390/mi9060307
  21. Sudareva NN, Suvorova OM, Suslov DN, Galibin OV, Vilesov AD (2021) Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats. Cell Ther Transplant 10: 71–77. https://doi.org/10.18620/ctt-1866–8836–2021–10–3–4–71–77
  22. Trushina DB, Bukreeva TV, Kovalchuk MV, Antipina MN (2014) CaCO₃ vaterite microparticles for biomedical and personal care applications. Mater Sci Eng C Mater Biol Appl 45: 644–658. https://doi.org/10.1016/j.msec.2014.04.050
  23. Wang C, He C, Tong Z, Liu X, Ren B, Zeng F (2006) Combination of adsorption by porous CaCO3 microparticles and encapsulation by polyelectrolyte multilayer films for sustained drug delivery. Int J Pharm 308: 160–167. https://doi.org/10.1016/j.ijpharm.2005.11.004
  24. Saveleva MS, Ivanov AN, Chibrikova JA, Abalymov AA, Surmeneva MA, Surmenev RA, Parakhonskiy BV, Lomova MV, Skirtach AG, Norkin IA (2021) Osteogenic capability of vaterite-coated nonwoven polycaprolactone scaffolds for in vivo bone tissue regeneration. Macromol Biosci 21: 2100266. https://doi.org/10.1002/mabi.202100266
  25. Dizaj SM, Barzegar-Jalali M, Hossein Zarrintan M, Adibkia K, Lotfipour F (2015) Calcium carbonate nanoparticles; potential in bone and tooth disorders. Pharm Sci 20: 175–182. https://doi.org/10.5681/PS.2015.008
  26. An S (2019) The emerging role of extracellular Ca2+ in osteo/odontogenic differentiation and the involvement of intracellular Ca2+ signaling: from osteoblastic cells to dental pulp cells and odontoblasts. J Cell Physiol 234: 2169–2193. https://doi.org/10.1002/jcp.27068
  27. Abalymov A, Lengert E, Van der Meeren L, Saveleva M, Ivanova A, Douglas TEL, Skirtach AG, Volodkin D, Parakhonskiy B (2022) The influence of Ca/Mg ratio on autogelation of hydrogel biomaterials with bioceramic compounds. Biomater Adv 133: 112632. https://doi.org/10.1016/j.msec.2021.112632
  28. Sergeeva A, Vikulina AS, Volodkin D (2019) Porous alginate scaffolds assembled using vaterite CaCO3 crystals. Micromachines (Basel) 10: 357. https://doi.org/10.3390/mi10060357
  29. Niu YQ, Liu JH, Aymonier C, Fermani S, Kralj D, Falini G, Zhou CH (2022) Calcium carbonate: controlled synthesis, surface functionalization, and nanostructured materials. Chem Soc Rev 51: 7883–7943. https://doi.org/10.1039/d1cs00519g
  30. Yu Q, Su B, Zhao W, Zhao C (2023) Janus self-propelled chitosan-based hydrogel spheres for rapid bleeding control. Adv Sci (Weinh) 10: 2205989. https://doi.org/10.1002/advs.202205989
  31. Li Q, Hu E, Yu K, Xie R, Lu F, Lu B, Bao R, Zhao T, Dai F, Lan G (2020) Self-propelling janus particles for hemostasis in perforating and irregular wounds with massive hemorrhage. Adv Funct Mater 30: 2004153. https://doi.org/10.1002/adfm.202004153
  32. Baylis JR, Yeon JH, Thomson MH, Kazerooni A, Wang X, St John AE, Lim EB, Chien D, Lee A, Zhang JQ, Piret JM, Machan LS, Burke TF, White NJ, Kastrup CJ (2015) Self-propelled particles that transport cargo through flowing blood and halt hemorrhage. Sci Adv 1: 1500379. https://doi.org/10.1126/sciadv.1500379
  33. Сampbell J, Ferreira AM, Bowker L, Hunt J, Volodkin D, Vikulina A (2022) Dextran and its derivatives: biopolymer additives for the modulation of vaterite CaCO3 crystal morphology and adhesion to cells. Advan Mater Interfac 9: 2201196. https://doi.org/10.1002/admi.202201196
  34. Mikhalchik EV, Basyreva LY, Gusev SA, Panasenko OM, Klinov DV, Barinov NA, Morozova OV, Moscalets AP, Maltseva LN, Filatova LY, Pronkin EA, Bespyatykh JA, Balabushevich NG (2022) Activation of neutrophils by mucin-vaterite microparticles. Int J Mol Sci 23: 10579. https://doi.org/10.3390/ijms231810579
  35. Mikhalchik EV, Maltseva LN, Firova RK, Murina MA, Gorudko IV, Grigorieva DV, Ivanov VA, Obraztsova EA, Klinov DV, Shmeleva EV, Gusev SA, Panasenko OM, Sokolov AV, Gorbunov NP, Filatova LY, Balabushevich NG (2023) Incorporation of pectin into vaterite microparticles prevented effects of adsorbed mucin on neutrophil activation. Int J Mol Sci 24: 15927. https://doi.org/10.3390/ijms242115927
  36. Kotova YN, Podoplelova NA, Obydennyy SI, Kostanova EA, Ryabykh AA, Demyanova AS, Biriukova MI, Rosenfeld MA, Sokolov AV, Chambost H, Kumskova MA, Ataullakhanov FI, Alessi MC, Panteleev MA (2019) Binding of coagulation factor XIII zymogen to activated platelet subpopulations: roles of integrin αIIbβ3 and fibrinogen. Thromb Haemost 119: 906–915. https://doi.org/10.1055/s-0039–1683912
  37. Gorudko IV, Sokolov AV, Shamova EV, Grudinina NA, Drozd ES, Shishlo LM, Grigorieva DV, Bushuk SB, Bushuk BA, Chizhik SA, Cherenkevich SN, Vasilyev VB, Panasenko OM (2013) Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry. Biol Open 2: 916–923. https://doi.org/10.1242/bio.20135314
  38. Lin Z, Tan X, Zhang Y, Li F, Luo P, Liu H (2020) Molecular targets and related biologic activities of fucoidan: a review. Mar Drugs 18: 376. https://doi.org/10.3390/md18080376
  39. Fitton JH (2011) Therapies from fucoidan; multifunctional marine polymers. Mar Drugs 9: 1731–1760. https://doi.org/10.3390/md9101731
  40. Fitton JH, Stringer DN, Karpiniec SS (2015) Therapies from fucoidan: an update. Mar Drugs 13: 5920–5946. https://doi.org/10.3390/md13095920
  41. Dubashynskaya NV, Gasilova ER, Skorik YA (2023) Nano-sized fucoidan interpolyelectrolyte complexes: recent advances in design and prospects for biomedical applications. Int J Mol Sci 24: 2615. https://doi.org/10.3390/ijms24032615
  42. Manne BK, Getz TM, Hughes CE, Alshehri O, Dangelmaier C, Naik UP, Watson SP, Kunapuli SP (2013) Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2). J Biol Chem 288: 7717–7726. https://doi.org/10.1074/jbc.M112.424473
  43. Qiu M, Huang S, Luo C, Wu Z, Liang B, Huang H, Ci Z, Zhang D, Han L, Lin J (2021) Pharmacological and clinical application of heparin progress: an essential drug for modern medicine. Biomed Pharmacother 139: 111561. https://doi.org/10.1016/j.biopha.2021.111561
  44. Kardeby C, Evans A, Campos J, Al-Wahaibi AM, Smith CW, Slater A, Martin EM, Severin S, Brill A, Pejler G, Sun Y, Watson SP (2023) Heparin and heparin proteoglycan-mimetics activate platelets via PEAR1 and PI3Kβ. J Thromb Haemost 21: 101–116. https://doi.org/10.1016/j.jtha.2022.10.008
  45. Chong BH, Ismail F (1989) The mechanism of heparin-induced platelet aggregation. Eur J Haematol 43: 245–251. https://doi.org/10.1111/j.1600–0609.1989.tb00290.x
  46. Ahmed I, Majeed A, Powell R (2007) Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J 83: 575–582. https://doi.org/10.1136/pgmj.2007.059188
  47. Brodard J, Alberio L, Angelillo-Scherrer A, Nagler M (2020) Accuracy of heparin-induced platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. Thromb Res 185: 27–30. https://doi.org/10.1016/j.thromres.2019.11.004
  48. Cipriani TR, Gracher AH, de Souza LM, Fonseca RJ, Belmiro CL, Gorin PA, Sassaki GL, Iacomini M (2009) Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects. Thromb Haemost 101: 860–866. https://doi.org/10.1160/TH08–08–0556
  49. Shen Q, Guo Y, Wang K, Zhang C, Ma Y (2023) A review of chondroitin sulfate's preparation, properties, functions, and applications. Molecules 28: 7093. https://doi.org/10.3390/molecules28207093
  50. Sakai T, Kyogashima M, Kariya Y, Urano T, Takada Y, Takada A (2000) Importance of GlcUAβ1–3GalNAc(4S,6S) in chondroitin sulfate E for t-PA- and u-PA-mediated Glu-plasminogen activation. Thromb Res 100: 557–565. https://doi.org/10.1016/S0049–3848(00)00365–0
  51. Maruyama T, Toida T, Imanari T, Yu G, Linhardt RJ (1998) Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation. Carbohydr Res 306: 35–43. https://doi.org/10.1016/S0008–6215(97)10060-X
  52. Nader HB (1991) Characterization of a heparan sulfate and a peculiar chondroitin 4-sulfate proteoglycan from platelets. Inhibition of the aggregation process by platelet chondroitin sulfate proteoglycan. J Biol Chem 266: 10518–10523. https://doi.org/10.1016/S0021–9258(18)99255–0
  53. Shen Q, Guo Y, Wang K, Zhang C, Ma Y (2023) A review of chondroitin sulfate's preparation, properties, functions, and applications. Molecules 28: 7093. https://doi.org/10.3390/molecules28207093
  54. Strasenburg W, Jóźwicki J, Durślewicz J, Kuffel B, Kulczyk MP, Kowalewski A, Grzanka D, Drewa T, Adamowicz J (2022) Tumor cell-induced platelet aggregation as an emerging therapeutic target for cancer therapy. Front Oncol 12: 909767. https://doi.org/10.3389/fonc.2022.909767
  55. Kato Y, Kaneko MK, Kunita A, Ito H, Kameyama A, Ogasawara S, Matsuura N, Hasegawa Y, Suzuki-Inoue K, Inoue O, Ozaki Y, Narimatsu H (2008) Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci 99: 54–61. https://doi.org/10.1111/j.1349–7006.2007.00634.x
  56. Vandenbriele C, Sun Y, Criel M, Cludts K, Van Kerckhoven S, Izzi B, Vanassche T, Verhamme P, Hoylaerts MF (2016) Dextran sulfate triggers platelet aggregation via direct activation of PEAR1. Platelets 27: 365–372. https://doi.org/10.3109/09537104.2015.1111321
  57. Hlady V (1984) Adsorption of dextran and dextran sulfate on precipitated calcium oxalate monohydrate. J Colloid and Interface Sci 98: 373–384. https://doi.org/10.1016/0021–9797(84)90161–9

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. The effect of the tested biopolymers on platelet aggregation in OTP. (a) and (c) are typical kinetic curves of platelet aggregation in OTP initiated by the introduction of fucoidan (a) or ADP in the presence of different concentrations of pectin (c). (b) and (d) are the dependence of the degree of spontaneous (b) or ADP–induced (d) platelet aggregation in OTP on the concentration of fucoidan, heparin and dextran sulfate (b) or pectin, mucin and chondroitin sulfate (d). The concentration of ADP used is 2.5 microns. To the right of the kinetic curves, the numbers indicate the concentrations of biopolymers used in micrograms/ml.

Download (221KB)
Indexing metadata
3. Fig. 2. The effect of native and biopolymer-functionalized waterite microparticles (250 mcg/ml) on spontaneous and ADP-induced platelet aggregation in OTP. The concentration of ADP is 2.5 microns. *p < 0.05 compared to the effect of native waterite microparticles. In the case of ADP-induced aggregation, the value of the degree of aggregation in the control was taken as 100% (with the addition of 2.5 microns of ADP). #p < 0.05 compared to the ADP effect.

Download (225KB)
Indexing metadata
4. Fig. 3. The effect of the tested biopolymers on the aggregation of isolated platelets. (a) and (c) are typical kinetic curves of aggregation of isolated platelets initiated by the introduction of mucin (a) or thrombin in the presence of different concentrations of dextran sulfate (c). (b) and (d) are the dependence of the degree of spontaneous (b) or thrombin–induced (d) aggregation of isolated platelets on the concentration of fucoidan, heparin and mucin (b) or pectin, dextran sulfate and chondroitin sulfate (d). The concentration of thrombin used is 1 mcg/ml. To the right of the kinetic curves, the numbers indicate the concentration of biopolymers used in micrograms/ml.

Download (243KB)
Indexing metadata
5. Fig. 4. The effect of native and biopolymer-functionalized waterite microparticles (250 mcg/ml) on spontaneous and thrombin-induced aggregation of isolated platelets. The concentration of thrombin is 1 microgram/ml. * p < 0.05 compared to the effect of native waterite microparticles. In the case of thrombin-induced aggregation, the value of the degree of aggregation in the control was taken as 100% (with the addition of 1 mcg/ml of thrombin). # p < 0.05 compared to the thrombin effect.

Download (225KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences