Preview

Fine Chemical Technologies

Advanced search

BIODEGRADABLE POLYMER MATERIALS FOR MEDICAL APPLICATIONS: FROM IMPLANTS TO ORGANS

https://doi.org/10.32362/2410-6593-2017-12-5-5-20

Abstract

Development of modern medical technologies would be impossible without the application of various materials with special properties. Over the last decade there has been a marked increase in interest in biodegradable materials for use in medicine and other areas of the national economy. In medicine, biodegradable polymers offer great potential for controlled drug delivery and wound management (e.g., adhesives, sutures and surgical meshes), for orthopedic devices (screws, pins and rods), nonwoven materials and scaffolds for tissue engineering. Among the family of biodegradable polyesters the most extensively investigated and the most widely used polymers are poly(α-hydroxyacid)s: polylactide (i.e. PLA), polyglycolide (i.e. PGA), poly-ε-caprolactone (PCL), polydioxanone and their copolymers. Controlling the molecular and supramolecular structure of biodegradable polymers allows tuning the physico-chemical and mechanical characteristics of the materials as well as their degradation kinetics. This enables selecting the optimal composition and structure of the material for the development of a broad range of biomedical products. Introduction of various functional fillers such as calcium phosphates allows creating bioactive composite materials with improved mechanical properties. To manufacture the highly dispersed biomedical materials for regenerative medicine electrospinning and freeze-drying are employed. Varying the technological parameters of the process enables to produce materials and devices with predetermined pore sizes and various mechanical properties. In order to increase the effectiveness of a great number of drugs the perspective approach is their inclusion into nanosized polymer micelles based on amphiphilic block copolymers of lactide and ethylene oxide. Different crystallization behavior of the lactide blocks and controlled regulation of their length allows producing micelles with various sizes and morphology. In this article we have attempted to provide an overview of works that are under way in the area of biodegradable polymers research and development in our group.

About the Authors

V. I. Gomzyak
Moscow Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); National Research Centre «Kurchatov Institute»
Russian Federation

Assistant of the Medvedev Chair of Chemistry and Technology of High-Molecular Compounds

86, Vernadskogo Pr., Moscow, 119571, Russia

Engineer-Researcher of the Laboratory of Polymeric Materials

1, Kurchatova Sq., Moscow, 123182, Russia



V. A. Demina
National Research Centre «Kurchatov Institute»
Russian Federation

Postgraduate Student,

1, Kurchatova Sq., Moscow, 123182, Russia



E. V. Razuvaeva
National Research Centre «Kurchatov Institute»
Russian Federation

Engineer-Researcher of the Laboratory of Polymeric Materials

1, Kurchatova Sq., Moscow, 123182, Russia



N. G. Sedush
Moscow Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); National Research Centre «Kurchatov Institute»
Russian Federation

Ph.D. (Physics and Mathematics), Researcher of the Medvedev Chair of Chemistry and Technology of High-Molecular Compounds

86, Vernadskogo Pr., Moscow, 119571, Russia

Engineer-Researcher of the Laboratory of Polymeric Materials

1, Kurchatova Sq., Moscow, 123182, Russia



S. N. Chvalun
Moscow Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies); National Research Centre «Kurchatov Institute»
Russian Federation

D.Sc. (Chemistry), Professor, Head of the Medvedev Chair of Chemistry and Technology of High-Molecular Compounds

86, Vernadskogo Pr., Moscow, 119571, Russia

Deputy Director of Kurchatov Complex of NBICS-Technologies,

1, Kurchatova Sq., Moscow, 123182, Russia



References

1. Shtilman M.I., Podkorytova A.V., Nemtsev S.V., Kriazhev V.N. / Ed. M.I. Shtilman. Technology of polymers for medical and biological purposes. Polymers of natural origin. Мoscow: Binom, 2015. 328 p. (in Russ.)

2. Biocompatible materials / Ed. V.I. Sevastyanov, M.P. Kirprchnikov. Мoscow: Meditsinskoe informatsionnoe agentstvo, 2011. 544 p. (in Russ.)

3. Charyshkin A.L., Glushchenko L.V., Chvalun S.N., Sedush N.S. Experimental investigation of selfsoluble cava-filter // Khirurgiya (Surgery). 2014. V. 10. P. 21–24. (in Russ.)

4. Kreuter J. Nanoparticulate systems for brain delivery of drugs // Adv. Drug Deliv. Rev. 2012. V. 64. P. 213–222.

5. Raya-Rivera A.M., Esquiliano D., Fierro-Pastrana R., López-Bayghen E., Valencia P., Ordorica-Flores R., Soker S., Yoo J.J.,Atala A. Tissue-engineered autologous vaginal organs in patients: a pilot cohort study // Lancet. 2014. V. 384. № 9940. P. 329–336.

6. Nicolas J., Mura S., Brambilla D., Mackiewicz N., Couvreur P. Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery // Chem. Soc. Rev. 2013. V. 42. № 3. P. 1147–1235.

7. Perego G., Cella G.D., Bastioli C. Effect of molecular weight and crystallinity on poly(lactic acid) mechanical properties // J. Appl. Polym. Sci. 1996. V. 59. № 1. P. 37–43.

8. Murariu M., Dubois P. PLA composites: From production to properties // Adv. Drug Deliv. Rev. 2016. V. 107. P. 17–46.

9. Bogdanova О.I., Sedush N.G., Ovchinnikova Т.N., Belousov S.I., Polyakov D.K., Chvalun S.N. Polylactide – biodegradable biocompatible polymer based on plant raw materials // Ekologiya i promyishlennost Rossii (Ecology and Industry of Russia). 2010. V. 5. P. 18–23. (in Russ.)

10. Tuominen J., Seppälä J.V. Synthesis and characterization of lactic acid based poly(ester−amide) // Macromolecules. 2000. V. 33. № 10. P. 3530–3535.

11. Moon S.I., Lee C.-W., Taniguchi I., Miyamoto M., Kimura Y.Melt/solid polycondensation of L-lactic acid: An alternative route to poly(L-lactic acid) with high molecular weight // Polymer (Guildf). 2001. V. 42. № 11. P. 5059–5062.

12. Zhang X., Macdonald D.A., Goosen F.A., McAuley K.B. Mechanism of lactide polymerization in the presence of stannous octoate: The effect of hydroxy and carboxylic acid substances // J. Polym. Sci. (Part A). 1994. V. 32. № 15. P. 2965–2970.

13. Kowalski A., Duda A., Penczek S. Kinetics and mechanism of cyclic esters polymerization initiated with tin(II) octoate. Polymerization of L,L-dilactide // Macromolecules. 2000. V. 33. № 20. P. 7359–7370.

14. Stridsberg K.M., Ryner M., Albertsson A. Controlled ring-opening polymerization: Polymers with designed macromolecular architecture // Degrad. Aliphatic Polyesters. Berlin, Heidelberg: Springer Berlin Heidelberg. 2002. V. 157. P. 41–65.

15. Kalb B., Pennings A.J. General crystallization behaviour of poly(L-lactic acid) // Polymer (Guildf). 1980. V. 21. № 6. P. 607–612.

16. Malafeev K.V., Moskalyuk О.А., Yudin V.E., Sedush N.G., Chvalun S.N., V.Yu. Elokhovskii, Popova E.N., Ivan’kova E.M. Preparation and properties of fibers from a copolymer of lactic and glycolic acids // Vyisokomolekulyarnyie Soedineniya (А) (HighMolecular Compounds (A)). 2017. V. 59. № 1. P. 1–6. (in Russ.)

17. Sedush N.G., Chvalun S.N. Kinetics and thermodynamics of L-lactide polymerization studied by differential scanning calorimetry // Eur. Polym. J. 2015.V. 62. P. 198–203.

18. Sedush N.G., Strelkov Y.Y., Chvalun S.N. Kinetic investigation of the polymerization of D,L-lactide and glycolide via differential scanning calorimetry // Vyisokomolekulyarnyie Soedineniya (B) (High-Molecular Compounds (B)). 2014. V. 56. P. 39–44. (in Russ.)

19. Middleton J.C., Tipton A.J. Synthetic biodegradable polymers as orthopedic devices // Biomaterials. 2000. V. 21. № 23. P. 2335–2346.

20. Agadzhanyan V.V., Pronskikh A.A., Demina V.A., Gomzyak V.I., Sedush N.G., Chvalun S.N. Biodegradable implants in orthopedics and traumatology. Our first experience // Politravma (Poly-Injury). 2016. V. 4. P. 85–93. (in Russ.)

21. Burg K.J., Porter S., Kellam J.F. Biomaterial developments for bone tissue engineering // Biomaterials. 2000. V. 21. № 23. P. 2347–2359.

22. Cancedda R., Dozin B., Giannoni P., Quarto R. Tissue engineering and cell therapy of cartilage and bone // Matrix Biol. 2003. V. 22. № 1. P. 81–91.

23. Yoshikawa H., Myoui A. Bone tissue engineering with porous hydroxyapatite ceramics // J. Artif. Organs. 2005. V. 8. № 3. P. 131–136.

24. Kalita S.J., Bhardwaj A., Bhatt H.A. Nanocrystalline calcium phosphate ceramics in biomedical engineering // Mater. Sci. Eng. C. 2007. V. 27. № 3. P. 441–449.

25. Dong Q., Chow L.C., Wang T., Frukhtbeyn S.A., Wang F., Yang M., Mitchel l J.W. A new bioactive polylactide-based composite with high mechanical strength // Colloids Surfaces A. 2014. V. 457. P. 256–262.

26. Bazhenov S.L., Berlin A.A., Kulkov A.A. Oshmian V.G. Polymer composite materials. Strength and technology. Dolgoprudnyj: Publ. House “Intellekt”, 2010. 347 p. (in Russ.)

27. Peer D., Karp J.M., Hong S., Farokhzad O.C., Margalit R., Langer R. Nanocarriers as an emerging platform for cancer therapy // Nat. Nanotechnol. 2007. V. 2. № 12. P. 751–760.

28. Balabanyan V., Ul’yanov A., Bojat V., Khomenko A., Sedush N., Chvalun S., Kapanadze G., Hamdy Y., Shvets V. Development and evaluation of a nanoparticulate paclitaxel formulation based on lacticglycolic acids copolymer // Biopharmaceutical Journal. 2013. № 6. P. 28–37. (in Russ.)

29. Nikol'skaya E.D., Zhunina O.A., Yabbarov N.G., Shvets V.I., Kruglyj B.I., Severin E.S. Development of direct delivery systems of antitumor drugs of actinomycin series with recombinant alpha-fetoprotein // Doklady Akademii nauk. 2017. V. 473. № 6. P. 739–741. (in Russ.)

30. Ivanov A.E., Zubov V.P. Smart polymers as surface modifiers for bioanalytical devices and biomaterials: Theory and practice// Uspekhi khimii (Russ. Chem. Rev.). 2016. V. 85. № 6. P. 565–584.

31. Wang Z.H., Wang Z.Y., Sun C.S., Wang C.Y., Jiang T.Y., Wang S.L. Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain // Biomaterials. 2010. V. 31. № 5. P. 908–915.

32. Tosi G., Constantino L., Ruozi B., Forni F., Vandelli M.A. Polymeric nanoparticles for the drug delivery to the central nervous system // Expert Opin. Drug Deliv. 2008. V. 5. № 2. P. 155–174.

33. Zhang J., Wang L.Q., Wang H., Tu K. Micellization phenomena of amphiphilic block copolymers based on methoxy poly(ethylene glycol) and either crystalline or amorphous poly(caprolactone-blactide) // Biomacromolecules. 2006. V. 7. P. 2492–2500.

34. Yang L., Zhao Z., Wei J., El Ghzaoui A., Li S. Micelles formed by self-organization of polylactide/poly(ethylene glycol) block copolymers in aqueous solutions // J. Colloid & Interface Sci. 2007. V. 314. P. 470–477.

35. Xiao R.Z., Zeng Z.W., Lin Zhou G., Wang J.J., Zhu Li F., Ming Wang A. Recent advances in PEG-PLA block copolymer nanoparticles // Int. J. Nanomedicine. 2010. V. 5. P. 1057–1065.

36. Riley T., Govender T., Stolnik S., Xiong C.D., Garnett M.C., Illum L., Davis S.S. Colloidal stability and drug incorporation aspects of micellar-like PLA-PEG nanoparticles // Colloids and Surfaces B: Biointerfaces. 1999. V. 16. P. 147–159.

37. Otsuka H., Nagasaki Y., Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications // Adv. Drug Deliv. Rev. 2003. V. 55. P. 403–419.

38. Zhao H., Liu Z., Park S., Kim S.H., Kim J.H., Piao L. Preparation and characterization of PEG/PLA multiblock and triblock copolymer // Bull. Korean Chem. Soc. 2012. V. 33. № 5. P. 1638–1642.

39. Perez C., Sanchez A., Putnam D., Ting D., Langer R., Alonso M.J. Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA // J. Contr. Release. 2001. V. 75. № 1-2. P. 211–224.

40. Posocco P., Fermeglia M., Pricl S. Morphology prediction of block copolymers for drug delivery by mesoscale simulations // J. Mater. Chem. 2010. V. 20. P.7742–7753.

41. Kelley E.G., Murphy R.P., Seppala J.E., Smart T.P., Hann S.D., Sullivan M.O., Epps T.H. Size evolution of highly amphiphilic macromolecular solution assemblies via a distinct bimodal pathway // Nature Commun. 2014. V. 5. № 3599. P. 1–10.

42. Fujiwara T., Miyamoto M., Kimura Y. Crystallization-induced morphological changes of a poly(L-lactide)/poly(oxyethylene) diblock copolymer from sphere to band via disk: A novel macromolecular self-organization process from core-shell nanoparticles on surface // Macromolecules. 2000. V. 33. P. 2782–2785.

43. Fujiwara T., Kimura Y. Macromolecular organization of poly(L-lactide)-block-polyoxyethylene into bio-inspired nano-architectures // Macromol. Biosci. 2002. V. 2. P. 11–23.

44. Sytina E.V., Tenchurin T.K., Rudyak S.G., Saprykin V.P., Romanova O.A., Orehov A.S., Vasiliev A.L., Alekseev A.A., Chvalun S.N., Paltsev M.A., Panteleyev A.A. Comparative biocompatibility of nonwoven polymer scaffolds obtained by electrospinning and their use for development of 3D dermal equivalents // Molekulyarnaya medicina (Molecular Medicine). 2014. № 6. P. 38–47. (in Russ.)

45. Lukanina K.I., Shepelev A.D., Budyka A.K. Synthesis of ultrafine fibers from L- and D,L-isomers of polylactide by electrospinning // Fibre Chemistry. 2012. V. 43 (5). P. 332–338.

46. Jain R. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices // Biomaterials. 2000. V. 21. № 23. P. 2475–2490.

47. Rodina A.V., Tenchurin T.K., Saprykin V.P., Shepelev A.D., Mamagulashvili V.G., Grigor'ev T.E., Moskaleva E.Yu., Chvalun S.N., Severin S.E. Proliferative and differentiation potential of multipotent mesenchymal stem cells on biocompatible polymer matrices with different physicochemical properties // Byulleten' eksperimental'noj biologii i mediciny (Bulletin of Experimental Biology and Medicine). 2016. V. 162. № 10. P. 486–494. (in Russ.)

48. Rodina A.V., Tenchurin T.K., Saprykin V.P., Shepelev A.D., Mamagulashvili V.G., Grigor'ev T.E., Lukanina K.I., Orekhov A.S., Moskaleva E.Y., Chvalun S.N. Migration and proliferative activity of mesenchymal stem cells in 3D polylactide scaffolds depends on cell seeding technique and collagen modification // Bull. Exp. Biology and Medicine. 2016. V. 162 (1). P. 120–126.

49. Kiselevsky M.V., Sitdikova S.M., Tenchurin T.K., Khomchenko A.Yu. Contemporary approaches and perspectives to creation of tracheal bioimplants // Rossijskij bioterapevticheskij zhurnal (Russian Biotherapeutics Journal). 2014. V. 13. № 3. P. 127–131. (in Russ.)

50. Kiselevsky M.V., Chikileva I.O., Vlasenko R.Ya., Sitdikova S.M., Tenchurin T.K., Mamagulashvili V.G., Shepelev A.D., Grigoriev T.E., Chvalun S.N. Biocompatibility of experimental polymeric tracheal matrices // Byulleten' eksperimental'noj biologii i mediciny (Bulletin of Experimental Biology and Medicine). 2016. V. 161. № 4. P. 528–531. (in Russ.)

51. Kiselevsky M.V., Anisimova N.Yu., Shepelev A.D., Tenchurin T.K., Mamagulashvili V.G., Krasheninnikov S.V., Grigoriev T.E., Lebedinskaya O.V., Chvalun S.N., Davydov M.I. Mechanical properties of a bioengineering prosthesis of a trachea based on a synthetic ultrafiber matrix // Rossijskij zhurnal biomekhaniki (Russian Journal of Biomechanics). 2016. V. 20. № 2. P. 116–122. (in Russ.)


Review

For citations:


Gomzyak V.I., Demina V.A., Razuvaeva E.V., Sedush N.G., Chvalun S.N. BIODEGRADABLE POLYMER MATERIALS FOR MEDICAL APPLICATIONS: FROM IMPLANTS TO ORGANS. Fine Chemical Technologies. 2017;12(5):5-20. (In Russ.) https://doi.org/10.32362/2410-6593-2017-12-5-5-20

Views: 2632


ISSN 2410-6593 (Print)
ISSN 2686-7575 (Online)