Synthesis and purification of poly(L-lactic acid) using a one step benign process

In this study, supercritical carbon dioxide (scCO2) was used as an alternative solvent for the synthesis and purification of poly(L-lactic acid) (PLLA) with a control on molecular weight. The synthesis of low molecular weight PLLA is desirable for applications such as drug delivery, resorbable implant applications and copolymerization of injectable polymer. Polymerizations were carried out in the presence of tin(II) 2-ethylhexanoate (Sn(Oct)2) and diethylene glycol (DEG) as catalyst and initiator, respectively. The resultant polymers were characterized and analysed by GPC, 1H NMR, ATR-FTIR, TGA and DSC. In particular, the effects of temperature, reaction time and pressure on polymer number average molecular weight (Mn), yield and polydispersity index (PDI) were investigated. Statistical analysis showed that temperature had the most significant effect on Mn, yield and PDI; this was followed by time and then pressure. An increase in temperature led to a significant increase in Mn, yield and PDI due to enhanced reactants solubility in CO2. Time and pressure had considerable effect on Mn and yield but not PDI. The optimum conditions for synthesising low molecular weight PLLA was 80 °C, 160 bar and 17 hours. Similar conditions were also tested and found to be efficient for removing the impurities. The results of this study demonstrated the feasibility of using a one pot process for the synthesis and purification of PLLA. We achieved high yield, very low PDI and tuneable Mn ranging from 1200 to 13 700 g mol−1 within the range examined. The process allowed eliminating the use of toxic organic solvent, stabilizer and esterification promoting agent. The synthesis of low molecular weight PLLA is desirable for applications such as drug delivery, resorbable implant applications and copolymerization of injectable polymer.

[1]  Y. Baimark,et al.  Effects of Arm Number and Arm Length on Thermal Properties of Linear and Star-shaped Poly(D,L-lactide)s , 2010 .

[2]  J. Rodríguez,et al.  Influence of the Operative Conditions on the Characteristics of Poly(D,L‐lactide‐co‐glycolide) Synthesized in Supercritical Carbon Dioxide , 2010 .

[3]  Jin Kuk Kim,et al.  Well-Controlled Microcellular Biodegradable PLA/Silk Composite Foams Using Supercritical CO2 , 2009 .

[4]  Kenji Yamane,et al.  Synthesis of polylactic acid by direct polycondensation under vacuum without catalysts, solvents and initiators , 2009 .

[5]  C. Jérôme,et al.  Synthesis of polylactide/clay nanocomposites by in situ intercalative polymerization in supercritical carbon dioxide , 2009 .

[6]  C. Yao,et al.  Manufacturing and Properties of PLA Absorbable Surgical Suture , 2008 .

[7]  R. Zare,et al.  Sustained release of drugs dispersed in polymer nanoparticles. , 2008, Angewandte Chemie.

[8]  J. Rodríguez,et al.  Kinetic Study of D,L‐Lactide and Glycolide Homopolymerizations by Differential Scanning Calorimetry , 2008 .

[9]  A. de Lucas,et al.  Copolymerization of D,L-lactide and glycolide in supercritical carbon dioxide with zinc octoate as catalyst. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[10]  K. Shakesheff,et al.  The effect of mesenchymal populations and vascular endothelial growth factor delivered from biodegradable polymer scaffolds on bone formation. , 2008, Biomaterials.

[11]  E. Jabbari,et al.  Synthesis and characterization of bioresorbable in situ crosslinkable ultra low molecular weight poly(lactide) macromer , 2008, Journal of materials science. Materials in medicine.

[12]  S. Einloft,et al.  Chemical synthesis and in vitro biocompatibility tests of poly (L-lactic acid). , 2007, Journal of biomedical materials research. Part A.

[13]  Pierre-Yves Zambelli,et al.  Repair of critical size defects in the rat cranium using ceramic-reinforced PLA scaffolds obtained by supercritical gas foaming. , 2007, Journal of biomedical materials research. Part A.

[14]  Shu-ying Gu,et al.  Preparation and characterization of porous PDLLA/HA composite foams by supercritical carbon dioxide technology. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[15]  K. Shakesheff,et al.  Supercritical carbon dioxide generated vascular endothelial growth factor encapsulated poly(DL-lactic acid) scaffolds induce angiogenesis in vitro. , 2007, Biochemical and biophysical research communications.

[16]  Won‐Ki Lee,et al.  Ring-opening polymerization of l-lactide in supercritical carbon dioxide using PDMS based stabilizers , 2007 .

[17]  S. Howdle,et al.  Novel fluorinated stabilizers for ring-opening polymerization in supercritical carbon dioxide , 2005 .

[18]  R. Jerome,et al.  Polymerization of (L,L)-lactide and copolymerization with epsilon-caprolactone initiated by dibutyltin dimethoxide in supercritical carbon dioxide , 2005 .

[19]  J. Verkade,et al.  Living polymerization of lactide using titanium alkoxide catalysts , 2005 .

[20]  S. Howdle,et al.  Tin(II) Ethyl Hexanoate Catalyzed Precipitation Polymerization of ∊-Caprolactone in Supercritical Carbon Dioxide , 2005 .

[21]  Odile Dechy-Cabaret,et al.  Controlled ring-opening polymerization of lactide and glycolide. , 2004, Chemical reviews.

[22]  Daniel Bratton,et al.  Direct synthesis of poly(l-lactic acid) in supercritical carbon dioxide with dicyclohexyldimethylcarbodiimide and 4-dimethylaminopyridine , 2004 .

[23]  Young Ha Kim,et al.  Effects of pressure and temperature on the kinetics of L-lactide polymerization in supercritical chlorodifluoromethane , 2004 .

[24]  K. Toshima,et al.  Lipase-catalyzed transformation of poly(lactic acid) into cyclic oligomers. , 2004, Macromolecular bioscience.

[25]  Young Ha Kim,et al.  Kinetic and Mechanistic Studies of l-Lactide Polymerization in Supercritical Chlorodifluoromethane , 2003 .

[26]  B H Alexander,et al.  Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility , 2003, Occupational and environmental medicine.

[27]  S. Howdle,et al.  Suspension Polymerization ofl-Lactide in Supercritical Carbon Dioxide in the Presence of a Triblock Copolymer Stabilizer , 2003 .

[28]  R. Singh,et al.  Laser based synthesis of nanofunctionalized particulates for pulmonary based controlled drug delivery applications , 2002 .

[29]  P. Tarantili,et al.  Synthesis and Characterization of Low Molecular Weight Polylactic Acid , 2002 .

[30]  I. Bechthold,et al.  Biodegradable polymers, 9: Technologically relevant aspects of kinetics and mechanism of ring-opening polymerization of L, L-dilactide , 2001 .

[31]  E. Pamuła,et al.  FTIR study of degradation products of aliphatic polyesters carbon fibres composites , 2001 .

[32]  A. Albertsson,et al.  Mechanism of Ring-Opening Polymerization of 1,5-Dioxepan-2-one and l-Lactide with Stannous 2-Ethylhexanoate. A Theoretical Study , 2001 .

[33]  M. Pishko,et al.  Emulsion copolymerization ofD,L-lactide and glycolide in supercritical carbon dioxide , 2001 .

[34]  R. Jerome,et al.  Ring-opening polymerization of ∈-caprolactone in supercritical carbon dioxide , 2001 .

[35]  M. Doxastakis,et al.  Controlled release systems based on poly(lactic acid). An in vitro and in vivo study , 2000, Journal of materials science. Materials in medicine.

[36]  Andrew I. Cooper,et al.  Polymer synthesis and processing using supercritical carbon dioxide , 2000 .

[37]  M. Pishko,et al.  Ring‐opening precipitation polymerization of poly(D,L‐lactide‐co‐glycolide) in supercritical carbon dioxide , 1999 .

[38]  A. Duda,et al.  Kinetics and Mechanism of Cyclic Esters Polymerization Initiated with Tin(II) Octoate. 3.† Polymerization of l,l-Dilactide , 1998 .

[39]  M. Ueda,et al.  Influence of the preparation methods on the drug release behaviour of loperamide-loaded nanoparticles. , 1998, Journal of microencapsulation.

[40]  S. Gogolewski,et al.  Effect of in vivo and in vitro degradation on molecular and mechanical properties of various low-molecular-weight polylactides. , 1997, Journal of biomedical materials research.

[41]  J. Seppälä,et al.  Synthesis and Characterization of Lactic Acid Based Telechelic Prepolymers , 1996 .

[42]  N. Manolova,et al.  NMR Analysis of Low Molecular Weight Poly(lactic acid)s , 1996 .

[43]  W C de Bruijn,et al.  Late degradation tissue response to poly(L-lactide) bone plates and screws. , 1995, Biomaterials.

[44]  P. Rohdewald,et al.  Low molecular weight PLA: a suitable polymer for pulmonary administered microparticles? , 1993, Journal of microencapsulation.

[45]  Y. Ikada,et al.  Lactic Acid Oligomer Microspheres Containing an Anticancer Agent for Selective Lymphatic Delivery: I. In Vitro Studies , 1988 .

[46]  N. Scharnagl,et al.  Poly(lactones). 9. Polymerization mechanism of metal alkoxide initiated polymerizations of lactide and various lactones , 1988 .