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Lipase-catalyzed copolymerization of lactic and glycolic acid with potential as drug delivery devices

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Abstract

The copolymerization of lactic and glycolic acid (PLGA) using Candida antarctica lipase B as biocatalyst has been achieved with the aim to generate useful biomedical materials. The influence of the reaction conditions, such as solvent and temperature, on the enzyme’s catalytic activity was studied to optimize the synthetic procedure. The evaluated parameters were the conversion, the isolated PLGA and the number average molecular weight (M n ). The identification and purity of the products were assessed by FTIR and NMR. The conversion was determined using analytical titration and the M n through end-group analysis. It was found that PLGA oligomers were obtained with satisfactory conversion levels when isopropyl ether was employed as solvent. The use of toluene increased the M n but decreased the isolated polyester. Higher percentages of recovered PLGA were reached increasing the temperature from 60 to 80 °C using toluene, while a reduction in the M n was evidenced under these conditions.

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References

  1. Shi G, Cai Q, Wang C, Lu N, Wang S, Be J (2002) Fabrication and biocompatibility of cell scaffolds of poly(l-lactic acid) and poly(l-lactic-co-glycolic acid). Polym Adv Technol 13:227–232

    Article  CAS  Google Scholar 

  2. Leenslag J, Pennings A, Bos R, Rozema F, Boering G (1987) Resorbable materials of poly(l-lactide): VII. In vivo and in vitro degradation. Biomaterials 8:311–314

    Article  CAS  Google Scholar 

  3. Kobayashi S (1999) Enzymatic polymerization: a new method of polymer synthesis. J Pol Sci Part A Pol Chem 37:3041–3056

    Article  CAS  Google Scholar 

  4. Matsumura S (2002) Enzyme catalyzed synthesis and chemical recycling of polyesters. Macromol Biosci 2:105–126

    Article  CAS  Google Scholar 

  5. Matsumura S (2006) Enzymatic synthesis of polyesters via ring opening polymerization. Adv Pol Sci 194:95–132

    Article  CAS  Google Scholar 

  6. Kiran K, Divakar S (2003) Lipase catalysed polymerization of lactic acid and its film forming properties. World J Microb Biotechnol 19:859–865

    Article  CAS  Google Scholar 

  7. Sonwalker R, Chen C, Ju L (2003) Roles of silica gel in polycondensation of lactic acid in organic solvent. Bioresour Technol 87:69–73

    Article  Google Scholar 

  8. Distel K, Zhu K, Wang G (2005) Biocatalysis using an organic soluble enzyme for the preparation of polylactic acid in organic solvents. Bioresour Technol 96:617–623

    Article  CAS  Google Scholar 

  9. Wahlberg J, Persson P, Olsson T, Hedestrom E, Iversen T (2003) Structural characterization of a lipase catalysed copolymerisation of ε-caprolactone and d,l-lactide. Biomacromolecules 4:1068–1071

    Article  CAS  Google Scholar 

  10. Huijser S, Staal B, Huang J, Duchateau R, Koning C (2006) Topology characterization by MALDI-ToF-MS of enzymatically synthesized poly(lactide-co-glycolide). Biomacromolecules 7:2465–2469

    Article  CAS  Google Scholar 

  11. Lassalle V, Ferreira M (2007) Enzymatic poly and co-polymerisation of lactic acid. In: Proceedings of 8th International Symposium on Biocatalysis and Biotransformations, Oviedo, Spain, p 23, 8–13 July 2007

  12. Allen P (1959) Techniques of polymer characterization. Butterworths, London, p 20

    Google Scholar 

  13. Wang N, Wu X, Lujan-Upton H (1997) Synthesis and characterization of lactic/glycolic acid oligomers. J Biomater Sci Polym Ed 8:905–917

    Article  CAS  Google Scholar 

  14. Dobrzynski P, Kasperczyk J, Janeczek H, Bero M (2001) Synthesis of biodegradable copolymers with the use of low toxic zirconium compounds. 1. Copolymerization of glycolide with l-lactide Initiated by Zr(Acac)4. Macromolecules 34:5090–5098

    Article  CAS  Google Scholar 

  15. Dobrzynski P, Kasperczyk J, Janeczek H, Bero M (2002) Synthesis of biodegradable glycolide/lactide copolymers using iron compounds as initiators. Polymer 42:2595–2601

    Article  Google Scholar 

  16. Kasperczyk J (1996) Microstructural analysis of poly[(l,l-lactide)-co-(glycolide)] by 1H and 13C n.m.r. spectroscopy. Polymer 37:201–203

    Article  CAS  Google Scholar 

  17. Schliecker G, Schmidt C, Fuchs S, Kissel T (2003) Characterization of a homologous series of d,l-lactic acid oligomers: a mechanistic study on the degradation kinetics in vitro. Biomaterials 24:3835–3844

    Article  CAS  Google Scholar 

  18. Shuai X, Jedlinski Z, Kowalczuk M, Rydz J, Ta H (1999) Enzymatic synthesis of polyesters from hydroxyl acids. Eur Polym J 35:721–25

    Article  CAS  Google Scholar 

  19. Engwicht A, Girreser A, Muller B (2000) Characterization of co-polymers of lactic and glycolic acid for supercritical fluid processing. Biomaterials 21:1587–1593

    Article  CAS  Google Scholar 

  20. Beletsi A, Leontiadis B, Klepetsanis P, Ithakissios D, Avgoustakis K (1999) Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide)-methoxypoly(ethylenglycol) copolymers related to their application in controlled drug delivery. Int J Pharm 182:187–197

    Article  CAS  Google Scholar 

  21. Kang M, Cho Y, Park K (2003) PLGA-PEG block copolymers for drug formulations. Drug Delivery Technology 3(5)

  22. Avgoustakis K, Nixon N (1991) Biodegradable controlled release tablets 1: preparative variables affecting the properties of poly(lactide-co-glycolide) copolymers as matrix forming material. Int J Pharm 70:77–85

    Article  CAS  Google Scholar 

  23. Bendix D (1997) Chemical synthesis of polylactide and its copolymers for medical applications. Polym Degrad Stability 59:129–135

    Article  Google Scholar 

  24. Hummel D, Scholl F (1988) Atlas of polymer and plastics analysis, 2nd edn, vol 2. Hanser, Munich, p 291

    Google Scholar 

  25. Varma I, Albertsson A, Rajkhowa R, Srivastava R (2005) Enzyme catalysed synthesis of polyesters. Prog Polym Sci 30:949–981

    Article  CAS  Google Scholar 

  26. Kumar A, Kalra B, Dekhterman A, Gross R (2000) Efficient ring opening polymerisation of caprolactone and pentadecalactone catalysed by Candida antactica Lipase B. Macromolecules 33:6303–6309

    Article  CAS  Google Scholar 

  27. Kumar A, Gross R (2000) Candida Antarctica Lipase B catalyzed polycaprolactone synthesis: effects of organic media and temperature. Biomacromolecules 1:133–138

    Article  CAS  Google Scholar 

  28. Ferruti P, Pence M, D’Addato P, Ranucci E, Deghenghi R (1995) Synthesis and properties of novel block copolymers containing poly(lactic-glycolic acid) and poly(ethyleneglyco1) segments. Biomaterials 16:1423–1428

    Article  CAS  Google Scholar 

  29. Dong H, Cao S, Li Z, Han S, You D, Shen J (1999) Study on the enzymatic polymerization mechanism of lactone and the strategy for improving the degree of polymerization. J Pol Sci Part A Pol Chem 37:1265–1275

    Article  CAS  Google Scholar 

  30. Al-Azhemi T, Kondaveti L, Bisht K (2002) Solventeless enantioselective ring-opening polymerization of substituted ε-caprolactones by enzymatic catalysis. Macromolecules 35:3380–3386

    Article  CAS  Google Scholar 

  31. Knani D, Gutman A, Kohn D (1993) Enzymatic polyesterification in organic media. Enzyme catalysed synthesis of linear polyesters. I. Condensation polymerization of linear hydroxyesters. II. Ring opening polymerization of ε-caprolactone. J Polym Sci Part A Pol Chem 31:1221–1232

    Article  CAS  Google Scholar 

  32. Kikuchi H, Uyama H, Kobayashi S (2000) Lipase catalysed enantioselective copolymerization of substituted lactones to optically active polyesters. Macromolecules 33:8971–8975

    Article  CAS  Google Scholar 

  33. Moon S, Lee C, Taniguchi I, Miyamoto M, Kimura Y (2001) Melt/solid polycondensation of l-lactic acid: an alternative route to poly(l-lactic acid) with high molecular weight. Polymer 42:5059–5062

    Article  CAS  Google Scholar 

  34. Takahashi K, Taniguchi I, Miyamoto M, Kimura Y (2000) Melt/solid polycondensation of glycolic acid to obtain high-molecular-weight poly(glycolic acid). Polymer 41:8725–8728

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the collaboration of Dr. Joao Henrique Zimnoch dos Santos and Cesar Petzhold from Universidade Federal do Rio Grande do Sul, Instituto de Química, Porto Alegre, Brazil and the financial support of National Research Council of Argentina (CONICET) and the University National of the South (UNS).

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Correspondence to Verónica Lassalle.

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Lassalle, V., Galland, G.B. & Ferreira, M.L. Lipase-catalyzed copolymerization of lactic and glycolic acid with potential as drug delivery devices. Bioprocess Biosyst Eng 31, 499–508 (2008). https://doi.org/10.1007/s00449-007-0188-y

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  • DOI: https://doi.org/10.1007/s00449-007-0188-y

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