Colloid and Polymer Science

, Volume 293, Issue 3, pp 913–923 | Cite as

Synthesis and micellization properties of triblock copolymers PDMAEMA-b-PCL-b-PDMAEMA and their applications in the fabrication of amphotericin B-loaded nanocontainers

Original Contribution
First Online:
Received:
Revised:
Accepted:

Abstract

In this study, we report the synthesis of PDMAEMA-b-PCL-b-PDMAEMA via ATRP starting from two dibromide-end polycaprolactone (PCL) of 2 and 10 kDa. The copolymerization was confirmed by nuclear magnetic resonance and gel permeation chromatography. The micellar properties of copolymers with different compositions were studied at pH 5.0, 6.0, 7.0, and 7.5. According to results, properties such as critical micellar concentration (CMC), hydrophobicity of micelle cores, and particle size strongly depend on the length of PCL. The pH shows an important effect on the size of the colloidal aggregates. Micelles obtained from copolymers with the lowest polymerization degree of both segments showed to be more appropriate for the encapsulation of amphotericin B (AmB).

Keywords

Polycaprolactone Block copolymer Micelles Atom transference radical polymerization 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgment

The authors thank the Pontificia Universidad Javeriana for financial support through grant number 5097.

References

  1. 1.
    Alexandridis P, Lindman B (2000) Amphiphilic block copolymers: self-assembly and applications. ElsevierGoogle Scholar
  2. 2.
    Torchilin VP (2001) Structure and design of polymeric surfactant-based drug delivery systems. J Control Release 73(2):137–172CrossRefGoogle Scholar
  3. 3.
    Loh XJ, Wu YL, Joseph Seow WT, Irzuan Norimzan MN, Zhang Z-X, Xu FJ, Kang ET, Neoh KG, Li J (2008) Micellization and phase transition behavior of thermosensitive poly (N-isopropylacrylamide)–poly(ε-caprolactone)–poly(N-isopropylacrylamide) triblock copolymers. Polymer 49(23):5084–5094. doi: 10.1016/j.polymer.2008.08.061 CrossRefGoogle Scholar
  4. 4.
    Yoon HJ, Jang WD (2010) Polymeric supramolecular systems for drug delivery. J Mater Chem 20(2):211–222CrossRefGoogle Scholar
  5. 5.
    Kore G, Kolate A, Nej A, Misra A (2014) Polymeric micelle as multifunctional pharmaceutical carriers. J Nanosci Nanotechnol 14(1):288–307. doi: 10.1166/jnn.2014.9021 CrossRefGoogle Scholar
  6. 6.
    Sinha V, Bansal K, Kaushik R, Kumria R, Trehan A (2004) Poly-ε-caprolactone microspheres and nanospheres: an overview. Int J Pharm 278(1):1–23CrossRefGoogle Scholar
  7. 7.
    Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32(8):762–798CrossRefGoogle Scholar
  8. 8.
    Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC (2005) Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 109(1):169–188CrossRefGoogle Scholar
  9. 9.
    Burt HM, Zhang X, Toleikis P, Embree L, Hunter WL (1999) Development of copolymers of poly (d,l-lactide) and methoxypolyethylene glycol as micellar carriers of paclitaxel. Colloids Surf B: Biointerfaces 16(1):161–171CrossRefGoogle Scholar
  10. 10.
    Shuai X, Ai H, Nasongkla N, Kim S, Gao J (2004) Micellar carriers based on block copolymers of poly (ε-caprolactone) and poly (ethylene glycol) for doxorubicin delivery. J Control Release 98(3):415–426CrossRefGoogle Scholar
  11. 11.
    Aliabadi HM, Elhasi S, Mahmud A, Gulamhusein R, Mahdipoor P, Lavasanifar A (2007) Encapsulation of hydrophobic drugs in polymeric micelles through co-solvent evaporation: the effect of solvent composition on micellar properties and drug loading. Int J Pharm 329(1):158–165CrossRefGoogle Scholar
  12. 12.
    Van de Wetering P, Cherng JY, Talsma H, Crommelin DJA, Hennink WE (1998) 2-(Dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents. J Control Release 53(1–3):145–153. doi: 10.1016/S0168-3659(97)00248-4 CrossRefGoogle Scholar
  13. 13.
    Zhang W, He J, Liu Z, Ni P, Zhu X (2010) Biocompatible and pH‐responsive triblock copolymer mPEG‐b‐PCL‐b‐PDMAEMA: synthesis, self‐assembly, and application. J Polym Sci A Polym Chem 48(5):1079–1091CrossRefGoogle Scholar
  14. 14.
    Xu FJ, Li H, Li J, Zhang Z, Kang ET, Neoh KG (2008) Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery. Biomaterials 29(20):3023–3033. doi: 10.1016/j.biomaterials.2008.03.041 CrossRefGoogle Scholar
  15. 15.
    Zhu C, Jung S, Luo S, Meng F, Zhu X, Park TG, Zhong Z (2010) Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA–PCL–PDMAEMA triblock copolymers. Biomaterials 31(8):2408–2416CrossRefGoogle Scholar
  16. 16.
    Xu F, Neoh K, Kang E (2009) Bioactive surfaces and biomaterials via atom transfer radical polymerization. Prog Polym Sci 34(8):719–761CrossRefGoogle Scholar
  17. 17.
    Qian X, Long L, Shi Z, Liu C, Qiu M, Sheng J, Pu P, Yuan X, Ren Y, Kang C (2014) Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma. Biomaterials 35(7):2322–2335. doi: 10.1016/j.biomaterials.2013.11.039 CrossRefGoogle Scholar
  18. 18.
    Lee AS, Gast AP, Bütün V, Armes SP (1999) Characterizing the structure of pH dependent polyelectrolyte block copolymer micelles. Macromolecules 32(13):4302–4310CrossRefGoogle Scholar
  19. 19.
    Baines F, Billingham N, Armes S (1996) Synthesis and solution properties of water-soluble hydrophilic-hydrophobic block copolymers. Macromolecules 29(10):3416–3420CrossRefGoogle Scholar
  20. 20.
    Liu S, Weaver JV, Tang Y, Billingham NC, Armes SP, Tribe K (2002) Synthesis of shell cross-linked micelles with pH-responsive cores using ABC triblock copolymers. Macromolecules 35(16):6121–6131CrossRefGoogle Scholar
  21. 21.
    Matyjaszewski K, Tsarevsky NV (2014) Macromolecular engineering by atom transfer radical polymerization. J Am Chem Soc 136(18):6513–6533. doi: 10.1021/ja408069v CrossRefGoogle Scholar
  22. 22.
    Ran J, Wu L, Zhang Z, Xu T (2014) Atom transfer radical polymerization (ATRP): a versatile and forceful tool for functional membranes. Prog Polym Sci 39(1):124–144. doi: 10.1016/j.progpolymsci.2013.09.001 CrossRefGoogle Scholar
  23. 23.
    Guo S, Qiao Y, Wang W, He H, Deng L, Xing J, Xu J, Liang XJ, Dong A (2010) Polycaprolactone-graft-poly(2-(N,N-dimethylamino) ethyl methacrylate) nanoparticles: pH dependent thermo-sensitive multifunctional carriers for gene and drug delivery. J Mater Chem 20(33):6935–6941. doi: 10.1039/C0JM00506A CrossRefGoogle Scholar
  24. 24.
    Lin D, Jiang Q, Cheng Q, Huang Y, Huang P, Han S, Guo S, Liang Z, Dong A (2013) Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery. Acta Biomater 9(8):7746–7757. doi: 10.1016/j.actbio.2013.04.031 CrossRefGoogle Scholar
  25. 25.
    Yue X, Qiao Y, Qiao N, Guo S, Xing J, Deng L, Xu J, Dong A (2010) Amphiphilic methoxy poly (ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-dimethylaminoethyl methacrylate) cationic copolymer nanoparticles as a vector for gene and drug delivery. Biomacromolecules 11(9):2306–2312. doi: 10.1021/bm100410m CrossRefGoogle Scholar
  26. 26.
    Zhang Y, He J, Cao D, Zhang M, Ni P (2014) Galactosylated reduction and pH dual-responsive triblock terpolymer Gal-PEEP-a-PCL-ss-PDMAEMA: a multifunctional carrier for the targeted and simultaneous delivery of doxorubicin and DNA. Polym Chem 5(17):5124–5138. doi: 10.1039/C4PY00538D CrossRefGoogle Scholar
  27. 27.
    Han S, Wan H, Lin D, Guo S, Dong H, Zhang J, Deng L, Liu R, Tang H, Dong A (2014) Contribution of hydrophobic/hydrophilic modification on cationic chains of poly(ε-caprolactone)-graft-poly(dimethylamino ethylmethacrylate) amphiphilic co-polymer in gene delivery. Acta Biomater 10(2):670–679. doi: 10.1016/j.actbio.2013.09.035 CrossRefGoogle Scholar
  28. 28.
    Lo YL, Chen GJ, Feng TH, Li MH, Wang LF (2014) Synthesis and characterization of S-PCL-PDMAEMA for co-delivery of pDNA and DOX. RSC Adv 4(22):11089–11098. doi: 10.1039/C3RA46914J CrossRefGoogle Scholar
  29. 29.
    Deray G (2002) Amphotericin B nephrotoxicity. J Antimicrob Chemother 49(suppl 1):37–41CrossRefGoogle Scholar
  30. 30.
    Rao JP, Geckeler KE (2011) Polymer nanoparticles: preparation techniques and size-control parameters. Prog Polym Sci 36(7):887–913CrossRefGoogle Scholar
  31. 31.
    Maiti S, Chatterji PR, Nisha C, Manorama S, Aswal VK, Goyal PS (2001) Aggregation and polymerization of PEG-based macromonomers with methacryloyl group as the only hydrophobic segment. J Colloid Interface Sci 240(2):630–635CrossRefGoogle Scholar
  32. 32.
    Shim WS, Kim SW, Choi EK, Park HJ, Kim JS, Lee DS (2006) Novel pH sensitive block copolymer micelles for solvent free drug loading. Macromol Biosci 6(2):179–186CrossRefGoogle Scholar
  33. 33.
    Motala-Timol S, Jhurry D (2007) Synthesis of PDMAEMA–PCL–PDMAEMA triblock copolymers. Eur Polym J 43(7):3042–3049CrossRefGoogle Scholar
  34. 34.
    San Miguel V, Limer A, Haddleton DM, Catalina F, Peinado C (2008) Biodegradable and thermoresponsive micelles of triblock copolymers based on 2-(N,N-dimethylamino) ethyl methacrylate and ε-caprolactone for controlled drug delivery. Eur Polym J 44(11):3853–3863CrossRefGoogle Scholar
  35. 35.
    Mok MM, Thiagarajan R, Flores M, Morse DC, Lodge TP (2012) Apparent critical micelle concentrations in block copolymer/ionic liquid solutions: remarkably weak dependence on solvophobic block molecular weight. Macromolecules 45(11):4818–4829CrossRefGoogle Scholar
  36. 36.
    Li X, Mya KY, Ni X, He C, Leong KW, Li J (2006) Dynamic and static light scattering studies on self-aggregation behavior of biodegradable amphiphilic poly (ethylene oxide)-poly [(R)-3-hydroxybutyrate]-poly (ethylene oxide) triblock copolymers in aqueous solution. J Phys Chem B 110(12):5920–5926CrossRefGoogle Scholar
  37. 37.
    Gohy JF (2005) Block copolymer micelles. In: Abetz V (ed) Block copolymers II, vol 190. Advances in polymer science. Springer, Berlin, pp 65–136. doi: 10.1007/12_048 CrossRefGoogle Scholar
  38. 38.
    Wilhelm M, Zhao CL, Wang Y, Xu R, Winnik MA, Mura JL, Riess G, Croucher MD (1991) Poly (styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study. Macromolecules 24(5):1033–1040. doi: 10.1021/ma00005a010 CrossRefGoogle Scholar
  39. 39.
    Allcock HR, Cho SY, Steely LB (2006) New amphiphilic poly [bis(2,2,2-trifluoroethoxy)phosphazene]/poly(propylene glycol) triblock copolymers: synthesis and micellar characteristics. Macromolecules 39(24):8334–8338. doi: 10.1021/ma061531w CrossRefGoogle Scholar
  40. 40.
    Nicolai T, Colombani O, Chassenieux C (2010) Dynamic polymeric micelles versus frozen nanoparticles formed by block copolymers. Soft Matter 6(14):3111–3118. doi: 10.1039/B925666K CrossRefGoogle Scholar
  41. 41.
    Zamfir M, Patrickios CS, Montagne F, Abetz C, Abetz V, Oss-Ronen L, Talmon Y (2012) Styrene-vinyl pyridine diblock copolymers: synthesis by RAFT polymerization and self-assembly in solution and in the bulk. J Polym Sci A Polym Chem 50(8):1636–1644CrossRefGoogle Scholar
  42. 42.
    Zhang X, Zhu X, Ke F, Ye L, EQ C, AY Z, ZG F (2009) Preparation and self-assembly of amphiphilic triblock copolymers with polyrotaxane as a middle block and their application as carrier for the controlled release of amphotericin B. Polymer 50(18):4343–4351CrossRefGoogle Scholar
  43. 43.
    van de Wetering P, Zuidam NJ, van Steenbergen MJ, van der Houwen OAGJ, Underberg WJM, Hennink WE (1998) A mechanistic study of the hydrolytic stability of poly(2-(dimethylamino)ethyl methacrylate). Macromolecules 31(23):8063–8068. doi: 10.1021/ma980689g CrossRefGoogle Scholar
  44. 44.
    Chen WY, Alexandridis P, Su CK, Patrickios CS, Hertler WR, Hatton TA (1995) Effect of block size and sequence on the micellization of ABC triblock methacrylic polyampholytes. Macromolecules 28(25):8604–8611. doi: 10.1021/ma00129a020 CrossRefGoogle Scholar
  45. 45.
    Tangeysh B, Fryd M, Ilies MA, Wayland BB (2012) Palladium metal nanoparticle size control through ion paired structures of [PdCl4]2− with protonated PDMAEMA. Chem Commun 48(71):8955–8957. doi: 10.1039/C2CC34401G CrossRefGoogle Scholar
  46. 46.
    Shim YH, Lee HJ, Dubois P, Chung CW, Jeong YI (2011) Amphotericin B aggregation inhibition with novel nanoparticles prepared with poly(ε-caprolactone)/poly(N,N-dimethylamino-2-ethyl methacrylate) diblock copolymer. J Microbiol Biotechnol 21(1):28–36CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Departamento de QuímicaPontificia Universidad JaverianaBogotáColombia
  2. 2.Departamento de QuímicaUniversidad Nacional de ColombiaBogotáColombia

Personalised recommendations