Skip to main content
SpringerLink
Log in

Random l-lactide/ε-caprolactone copolymers as drug delivery materials

  • Published:
Journal of Materials Science Aims and scope Submit manuscript

Abstract

In this work, the degradation phenomena and the release kinetics of an active molecule from matrices systems made of random copolymers of ε-caprolactone (CL) and l-lactide (LA) were investigated by exposing the matrices, shaped as thin films, to simulated physiological environments. α-tocopherol was incorporated into the films as hydrophobic model molecule with the aim to investigate both its release pattern and its effect on erosion phenomena. In particular, the films have been kept at controlled conditions (temperature, stirring, pH) and they were characterized in terms of weight loss, water uptake, thermal properties, and change of number average molecular weight, in order to explain the molecule release kinetics and the degradation pathways of the copolymers. The main findings of this study are that the erosion phenomena take place significantly only when a critical value of the molecular mass was obtained in the sample; that the presence of the drug stabilizes the matrix and it decreases the rate of molecular mass decrease; and that crystallinity, reducing the chain mobility, causes lower erosion rates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Notes

  1. Transesterification is the process of exchanging the alkoxy groups between polymer chains. There are two types of transesterification reaction: intramolecular leading to formation of cyclic oligomers and intermolecular leading to an increase in the range of chain lengths.

References

  1. Ye WP, Du FS, Jin WH, Yang JY, Xu Y (1997) In vitro degradation of poly(caprolactone), poly(lactide) and their block copolymers: influence of composition, temperature and morphology. React Funct Polym 32:161–168

    Article  Google Scholar 

  2. Huang MH, Li S, Hutmacher DW, Coudane J, Vert M (2006) Degradation characteristics of poly(α-caprolactone)-based copolymers and blends. J Appl Polym Sci 102:1681–1687

    Article  Google Scholar 

  3. Albertsson A-C, Varma IK (2003) Recent developments in ring opening polymerization of lactones for biomedical applications. Biomacromolecules 4:1466–1486

    Article  Google Scholar 

  4. Huang M-H, Li S, Vert M (2004) Synthesis and degradation of PLA–PCL–PLA triblock copolymer prepared by successive polymerization of ε-caprolactone and dl-lactide. Polymer 45:8675–8681

    Article  Google Scholar 

  5. Kister G, Cassanas G, Bergounhon M, Hoarau D, Vert M (2000) Structural characterization and hydrolytic degradation of solid copolymers of d,l-lactide-co-ε-caprolactone by Raman spectroscopy. Polymer 41:925–932

    Article  Google Scholar 

  6. Frank A, Rath SK, Venkatraman SS (2005) Controlled release from bioerodible polymers: effect of drug type and polymer composition. J Controlled Release 102:333–344

    Article  Google Scholar 

  7. Dash TK, Konkimalla VB (2012) Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Controlled Release 158:15–33

    Article  Google Scholar 

  8. Lao LL, Venkatraman SS (2008) Paclitaxel release from single and double-layered poly (dl-lactide-co-glycolide)/poly (l-lactide) film for biodegradable coronary stent application. J Biomed Mater Res Part A 87:1–7

    Article  Google Scholar 

  9. Wang S, Chen H, Cai Q, Bei J (2001) Degradation and 5-fluorouracil release behavior in vitro of polycaprolactone/poly (ethylene oxide)/polylactide tri-component copolymer. Polym Adv Technol 12:253–258

    Article  Google Scholar 

  10. Garkhal K, Verma S, Jonnalagadda S, Kumar N (2007) Fast degradable poly (l-lactide-co-ε-caprolactone) microspheres for tissue engineering: Synthesis, characterization, and degradation behavior. J Polym Sci Part A 45:2755–2764

    Article  Google Scholar 

  11. Hu Y, Jiang X, Ding Y et al (2003) Preparation and drug release behaviors of nimodipine-loaded poly (caprolactone)–poly (ethylene oxide)–polylactide amphiphilic copolymer nanoparticles. Biomaterials 24:2395–2404

    Article  Google Scholar 

  12. D’Auria I, Lamberti M, Mazzeo M, Milione S, Roviello G, Pellecchia C (2012) Coordination chemistry and reactivity of zinc complexes supported by a phosphido pincer ligand, chemistry-A. Eur J 18:2349–2360

    Article  Google Scholar 

  13. Manzanarez-López F, Soto-Valdez H, Auras R, Peralta E (2011) Release of α-tocopherol from poly(lactic acid) films, and its effect on the oxidative stability of soybean oil. J Food Eng 104:508–517

    Article  Google Scholar 

  14. Renò F, Aina V, Gatti S, Cannas M (2005) Effect of vitamin E addition to poly(d,l)-lactic acid on surface properties and osteoblast behaviour. Biomaterials 26:5594–5599

    Article  Google Scholar 

  15. Fischer E, Sterzel HJ, Wegner G (1973) Investigation of the structure of solution grown crystals of lactide copolymers by means of chemical reactions. Kolloid-Zeitschrift und Zeitschrift für Polymere 251:980–990

    Article  Google Scholar 

  16. Crescenzi V, Manzini G, Calzolari G, Borri C (1972) Thermodynamics of fusion of poly-β-propiolactone and poly-ε-caprolactone. Comparative analysis of the melting of aliphatic polylactone and polyester chains. Eur Polym J 8:449–463

    Article  Google Scholar 

  17. Palard I, Schappacher M, Belloncle B, Soum A, Guillaume SM (2007) Unprecedented polymerization of trimethylene carbonate initiated by a samarium borohydride complex: mechanistic insights and copolymerization with ε-caprolactone. Chem A Eur J 13:1511–1521

    Article  Google Scholar 

  18. Barba AA, Chirico S, Dalmoro A, Lamberti G (2009) Simultaneous measurement of theophylline and cellulose acetate phthalate in phosphate buffer by UV analysis. Can J Anal Sci Spectrscop 53:249–253

  19. Darensbourg DJ, Karroonnirun O (2010) Ring-opening polymerization of l-lactide and ε-caprolactone utilizing biocompatible zinc catalysts. Random copolymerization of l-lactide and ε-caprolactone. Macromolecules 43:8880–8886

    Article  Google Scholar 

  20. Li G, Lamberti M, Pappalardo D, Pellecchia C (2012) Random copolymerization of ε-caprolactone and lactides promoted by pyrrolylpyridylamido aluminum complexes. Macromolecules 45:8614–8620

    Article  Google Scholar 

  21. Florczak M, Duda A (2008) Effect of the configuration of the active center on comonomer reactivities: the case of ε-caprolactone/l, l-lactide copolymerization. Angew Chem Int Ed 47:9088–9091

    Article  Google Scholar 

  22. Nomura N, Akita A, Ishii R, Mizuno M (2010) Random copolymerization of ε-caprolactone with lactide using a Homosalen–Al complex. J Am Chem Soc 132:1750–1751

    Article  Google Scholar 

  23. Vanhoorne P, Dubois P, Jerome R, Teyssie P (1992) Macromolecular engineering of polylactones and polylactides. 7. Structural analysis of copolyesters of iε-caprolactone and l- or d,l-lactide initiated by triisopropoxyaluminum. Macromolecules 25:37–44

    Article  Google Scholar 

  24. Faÿ F, Renard E, Langlois V, Linossier I, Vallée-Rehel K (2007) Development of poly(ε-caprolactone-co-l-lactide) and poly(ε-caprolactone-co-δ-valerolactone) as new degradable binder used for antifouling paint. Eur Polym J 43:4800–4813

    Article  Google Scholar 

  25. Miller-Chou BA, Koenig JL (2003) A review of polymer dissolution. Prog Polym Sci 28:1223–1270

    Article  Google Scholar 

  26. Grayson ACR, Cima MJ, Langer R (2005) Size and temperature effects on poly (lactic-co-glycolic acid) degradation and microreservoir device performance. Biomaterials 26:2137–2145

    Article  Google Scholar 

  27. Park TG (1994) Degradation of poly (d,l-lactic acid) microspheres: effect of molecular weight. J Controlled Release 30:161–173

    Article  Google Scholar 

  28. Husmann M, Schenderlein S, Lück M, Lindner H, Kleinebudde P (2002) Polymer erosion in PLGA microparticles produced by phase separation method. Int J Pharm 242:277–280

    Article  Google Scholar 

  29. Gonçalves CMB, Tomé LC, Coutinho JAP, Marrucho IM (2011) Addition of α-tocopherol on poly(lactic acid): thermal, mechanical, and sorption properties. J Appl Polym Sci 119:2468–2475

    Article  Google Scholar 

  30. Antheunis H, van der Meer J-C, de Geus M, Kingma W, Koning CE (2009) Improved mathematical model for the hydrolytic degradation of aliphatic polyesters. Macromolecules 42:2462–2471

    Article  Google Scholar 

  31. Tsuji H, Ikada Y (1998) Blends of aliphatic polyesters. II. Hydrolysis of solution-cast blends from poly (l-lactide) and poly (E-caprolactone) in phosphate-buffered solution. J Appl Polym Sci 67:405–415

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Ministero dell’Istruzione dell’Università e della Ricerca-MIUR (contract grant number PRIN 2010/2011-20109PLMH2). Annalisa Dalmoro’s research grant was supported by “Strategie Terapeutiche Innovative”—STRAIN, POR Campania FSE 2007/2013. The Authors thank dr Ilaria D’Auria for the GPC measurements.

Author information

Authors and Affiliations

  1. Dipartimento di Farmacia, DIFARMA, Università degli Studi di Salerno, via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy

    Annalisa Dalmoro & Anna Angela Barba

  2. Dipartimento di Chimica e Biologia, DCB, Università degli Studi di Salerno, via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy

    Marina Lamberti, Mina Mazzeo & Vincenzo Venditto

  3. Dipartimento di Ingegneria Industriale, DIIn, Università degli Studi di Salerno, via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy

    Gaetano Lamberti

Authors
  1. Annalisa Dalmoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Angela Barba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marina Lamberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mina Mazzeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vincenzo Venditto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gaetano Lamberti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Angela Barba.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dalmoro, A., Barba, A.A., Lamberti, M. et al. Random l-lactide/ε-caprolactone copolymers as drug delivery materials. J Mater Sci 49, 5986–5996 (2014). https://doi.org/10.1007/s10853-014-8317-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10853-014-8317-x

Keywords

Search

Navigation