Synthesis of medical grade PLLA, PDLLA, and PLGA by a reactive extrusion polymerization

[en] Due to their biodegradability and biocompatibility, aliphatic polyesters received a considerable attention for a wide range of applications, in particular in medical and pharmaceutical fields. Aliphatic polyesters are usually synthesized by ring opening polymerization in a batch mode. In this work, a reactive extrusion polymerization was optimized to synthesise in a continuous way poly-L-lactide, poly-D,L-lactide, and poly-D,L-lactide-co-glycolide 50:50. A lab scale co-rotating twin screw extruder adapted for pharmaceutical products and medical devices was used after optimizing the geometry of screws and barrel. Polymerization was conducted in the presence of tin(II) 2-ethylhexanoate as catalyst and a monohydroxylated polyethylene glycol as initiator. The optimized procedure allowed producing high molecular weight polyesters (Mn in the range [15−100 kDa]) in a controlled way on a time scale of some minutes, with a capacity of at least 100 g/h and with monomer residues lower than 5%. Comparison of macromolecular features and thermal properties of the resulting polyesters of different Mn with those prepared in a batch process allowed concluding to the similarity of these materials. Reactive extrusion polymerization represents therefore a very attractive methodology to produce in a continuous, rapid and robust way aliphatic polyesters suitable for a wide range of pharmaceutical, medical or nowadays applications.

Research Center/Unit :

CEIB - Centre Interfacultaire des Biomatériaux - ULiège

Disciplines :

Materials science & engineering

Author, co-author :

Regibeau, Nicolas ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine

Hurlet, Jérôme ; Université de Liège - ULiège > CEIB

Tilkin, Rémi ; Université de Liège - ULiège > Department of Chemical Engineering > Nanomaterials, Catalysis, Electrochemistry

Lombart, François

Heinrichs, Benoît ; Université de Liège - ULiège > Department of Chemical Engineering > Génie chimique - Nanomatériaux et interfaces

Grandfils, Christian ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine

Language :

English

Title :

Synthesis of medical grade PLLA, PDLLA, and PLGA by a reactive extrusion polymerization

Publication date :

07 May 2020

Journal title :

Materials Today Communications

eISSN :

2352-4928

Publisher :

Elsevier, Oxford, United Kingdom

Volume :

Pages :

101208

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture

Available on ORBi :

since 10 June 2020

Statistics

Number of views

132 (22 by ULiège)

Number of downloads

11 (9 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Suzuki, S., Ikada, Y., Medical applications. Auras, R., Lim, L.-T., Selke, S.E.M., Tsuji, H., (eds.) Poly(Lactic Acid) Synth. Struct. Porperties, Process. Appl., 2010, John Wiley & Sons, Inc., 445–455, 10.1002/9780470649848.ch27.
Masutani, K., Kimura, Y., PLA synthesis. From the monomer to the polymer. Jiménez, A., Peltzer, M.A., Ruseckaite, R.A., (eds.) Poly(Lactic Acid)Science Technol. Process. Prop. Addit. Appl., 2015, Royal Society of Chemistry – Polymer Chemistry Series, 3–35, 10.1039/9781782624806-00001.
Nampoothiri, K.M., Nair, N.R., John, R.P., An overview of the recent developments in polylactide (PLA) research. Bioresour. Technol. 101 (2010), 8493–8501, 10.1016/j.biortech.2010.05.092.
Erbetta, C.D.C., Alves, R.J., Resende, J.M., de S. Freitas, R.F., de Sousa, R.G., Synthesis and characterization of poly(D,L-lactide-co-glycolide) copolymer. J. Biomater. Nanobiotechnol. 3 (2012), 208–225, 10.4236/jbnb.2012.32027.
Bendix, D., Chemical synthesis of polylactide and its copolymers for medical applications. Polym. Degrad. Stab. 59 (1998), 129–135, 10.1016/S0141-3910(97)00149-3.
Farah, S., Anderson, D.G., Langer, R., Physical and mechanical properties of PLA, and their functions in widespread applications – a comprehensive review. Adv. Drug Deliv. Rev. 107 (2016), 367–392, 10.1016/j.addr.2016.06.012.
Ramot, Y., Haim-Zada, M., Domb, A.J., Nyska, A., Biocompatibility and safety of PLA and its copolymers. Adv. Drug Deliv. Rev. 107 (2016), 153–162, 10.1016/j.addr.2016.03.012.
Gentile, P., Chiono, V., Carmagnola, I., Hatton, P.V., An overview of poly(lactic-co-glycolic) Acid (PLGA)-based biomaterials for bone tissue engineering. Int. J. Mol. Sci. 15 (2014), 3640–3659, 10.3390/ijms15033640.
Raquez, J.M., Degée, P., Nabar, Y., Narayan, R., Dubois, P., Biodegradable materials by reactive extrusion: from catalyzed polymerization to functionalization and blend compatibilization. Comptes Rendus Chim. 9 (2006), 1370–1379, 10.1016/j.crci.2006.09.004.
Jacobsen, S., Fritz, H.-G., Degée, P., Dubois, P., Jérôme, R., Continuous reactive extrusion polymerization of L-lactide – an engineering view. Macromolar Symp. 273 (2000), 261–273, 10.1002/1521-3900(200003)153:1<261::AID-MASY261>3.0.CO;2-9.
Södergard, A., Stolt, M., Industrial production of High molecular weight poly(lactic acid). Auras, R., Lim, L.-T., Selke, S.E.M., Tsuji, H., (eds.) Poly(Lactic Acid) Synth. Struct. Porperties, Process. Appl., 2010, John Wiley & Sons, Inc., 27–41, 10.1002/9780470649848 ch3.
Raquez, J.-M., Ramy-Ratiarison, R., Murariu, M., Dubois, P., reactive extrusion of PLA-based materials: from synthesis to reactive melt-blending. Jiménez, A., Peltzer, M.A., Ruseckaite, R.A., (eds.) Poly(Lactic Acid)Science Technol. Process. Prop. Addit. Appl., 2015, Royal Society of Chemistry – Polymer Chemistry Series, 101–122, 10.1039/9781782624806-00099.
Jacobsen, S., Fritz, H.G., Degée, P., Dubois, P., Jérôme, R.J., Single-step reactive extrusion of PLLA in a corotating twin-screw extruder promoted by 2-ethylhexanoic acid tin(II) salt and triphenylphosphine. Polymer (Guildf). 41 (2000), 3395–3403, 10.1016/S0032-3861(99)00507-8.
Gallos, A., Fontaine, G., Bourbigot, S., Reactive extrusion of stereocomplexed poly-L, d -Lactides: processing, characterization, and properties. Macromol. Mater. Eng. 298 (2013), 1016–1023, 10.1002/mame.201200271.
Hopmann, C., Adamy, M., Cohnen, A., Introduction to reactive extrusion. Beyer, G., Hopmann, C., (eds.) React. Extrus., 2017, Wiley-VCH, 3–9, 10.1002/9783527801541.ch1.
FDA, FDA - Code of Federal Regulations Title. 2018, 21 (accessed January 19, 2020) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=175.105&SearchTerm=ethylhexanoate.
Kricheldorf, H.R., Kreiser-Saunders, I., Boettcher, C., Polylactones, 31, Sn(II)octoate-initiated polymerization of L-lactide: a mechanistic study. Polymer (Guildf). 36 (1995), 1253–1259, 10.1016/0032-3861(95)93928-F.
Bourbigot, S., Fontaine, G., Gallos, A., Bellayer, S., Reactive extrusion of PLA and of PLA/carbon nanotubes nanocomposite: processing, characterization and flame retardancy. Polym. Adv. Technol. 22 (2011), 30–37, 10.1002/pat.1715.
Dubey, S.P., Abhyankar, H.A., Marchante, V., Brighton, J.L., Blackburn, K., Temple, C., Bergmann, B., Trinh, G., David, C., Modelling and validation of synthesis of poly lactic acid using an alternative energy source through a continuous reactive extrusion process. Polymers (Basel)., 8, 2016, 10.3390/polym8040164.
K. Jansson, J. Koskinen, J.-F. Selin, Process for the polymerization of lactide, WO1998036008A1, 2001. https://patents.google.com/patent/WO1998036008A1.
Z. Li, P. Ouyang, H. Huang, Method of making polylactide acid and its products, US8241545B2, 2011. https://patents.google.com/patent/US8241545/3Den.
D. Reichert, F.D. Klingler, H. Schwall, A. Christmann, B. Buchholz, Continuous process for the preparation of resorable polyesters and the use thereof, US5378801A, 1995. https://patents.google.com/patent/US5378801A/en.
Groot, W., Van Krieken, J., Sliekersl, O., De Vos, S., Production and purification of lactic acid and lactide. Auras, R., Lim, L.-T., Selke, S.E.M., Tsuji, H., (eds.) Poly(Lactic Acid) Synth. Struct. Porperties, Process. Appl., 2010, John Wiley & Sons, Inc., 3–18, 10.1002/9780470649848.ch1.
Fambri, L., Migliaresi, C., Cristallization and thermal properties. Auras, R., Lim, L.-T., Selke, S.E.M., Tsuji, H., (eds.) Poly(Lactic Acid) Synth. Struct. Porperties, Process. Appl., 2010, John Wiley & Sons, Inc., 113–124, 10.1002/9780470649848.ch9.
Janssen, L.P.B.M., Reactive Extrusion System. 2004, Marcel Dekker, Inc, 10.1201/9780203014172.
Lechner, F., The Co-rotating twin-screw extruder for reactive extrusion. Beyer, G., Hopmann, C., (eds.) React. Extrus., 2017, Wiley-VCH, 13–35, 10.1002/9783527801541.ch2.
Gautam, A., Choudhury, G.S., Screw configuration effects on residence time distribution and mixing in twin-screw extruder during extrusion of rice flour. J. Food Process Eng. 22 (1999), 263–285, 10.1111/j.1745-4530.1999.tb00485.x.
H.-G. Fritz, S. Jacobsen, R. Jérôme, P. Degée, P. Dubois, Aliphatic polyesters and/or copolyesters and a process for the production thereof, US6166169A, 2000. https://patents.google.com/patent/US6166169A/en.
Nijenhuis, A.J., Grijpma, D.W., Pennings, A.J., Lewis acid catalyzed polymerization of L-Lactide. Kinetics and mechanism of the bulk polymerization. Macromolecules. 25 (1992), 6419–6424, 10.1021/ma00050a006.
Bassi, M.B., Padias, A.B., Hall, H.K., The hydrolytic polymerization of ε-caprolactone by triphenyltin acetate. Polym. Bull. Berl. (Berl) 24 (1990), 227–232, 10.1007/BF00297322.
Sedush, N.G., Strelkov, Y.Y., Chvalun, S.N., Kinetic investigation of the polymerization of D,L-lactide and glycolide via differential scanning calorimetry. Polym. Sci. Ser. B. 56 (2014), 35–40, 10.1134/s1560090414010102.
Dorgan, J.R., Rheology of poly(lactic acid). Auras, R., Lim, L.-T., Selke, S.E.M., Tsuji, H., (eds.) Poly(Lactic Acid) Synth. Struct. Porperties, Process. Appl., 2010, John Wiley & Sons, Inc., 125–139, 10.1002/9780470649848.ch10.
Dorgan, J.R., Williams, J.S., Lewis, D.N., Melt rheology of poly(lactic acid): entanglement and chain architecture effects. J. Rheol. (N. Y. N. Y). 43 (2002), 1141–1155, 10.1122/1.551041.
Khodabakhshi, K., Ehsani, M., Development and applications of sustainable polylactic acid parts. Thakur, V.K., Thakur, M.K., (eds.) Handb. Sustain. Polym. Process. Anf Appl., 2016, Pan Stanford Publisher, 10.1201/b19948 pp. 429–424.
Garlotta, D., A literature review of poly(lactic acid). J. Polym. Environ., 9, 2002 doi:1566-2543/01/0400-0063/0.
Li, F.J., Zhang, S.D., Liang, J.Z., Wang, J.Z., Effect of polyethylene glycol on the crystallization and impact properties of polylactide-based blends. Polym. Adv. Technol. 26 (2015), 465–475, 10.1002/pat.3475.
Kulinski, Z., Piorkowska, E., Crystallization, structure and properties of plasticized poly(L-lactide). Polymer (Guildf). 46 (2005), 10290–10300, 10.1016/j.polymer.2005.07.101.
Bijarimi, M., Ahmad, S., Rasid, R., Khushairi, M.A., Zakir, M., Poly(lactic acid)/Poly(ethylene glycol) blends: mechanical, thermal and morphological properties. Int. Adv. Appl. Phys. Mater. Sci. Congr. Exhib., 2016, 10.1063/1.4945957.
Hassouna, F., Raquez, J., Addiego, F., Dubois, P., Toniazzo, V., Ruch, D., New approach on the development of plasticized polylactide (PLA): grafting of poly(ethylene glycol) (PEG) via reactive extrusion. Eur. Polym. J. 47 (2011), 2134–2144, 10.1016/j.eurpolymj.2011.08.001.
Feng, L., Zhang, B., Bian, X., Li, G., Chen, Z., Chen, X., Thermal properties of Polylactides with different stereoisomers of lactides used as comonomers. Macromolecules. 50 (2017), 6064–6073, 10.1021/acs.macromol.7b00818.