Skip to main content
SpringerLink
Log in

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
  • Published:
Colloid and Polymer Science Aims and scope Submit manuscript

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).

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Alexandridis P, Lindman B (2000) Amphiphilic block copolymers: self-assembly and applications. Elsevier

  2. Torchilin VP (2001) Structure and design of polymeric surfactant-based drug delivery systems. J Control Release 73(2):137–172

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  4. Yoon HJ, Jang WD (2010) Polymeric supramolecular systems for drug delivery. J Mater Chem 20(2):211–222

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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):1–23

    Article  CAS  Google Scholar 

  7. Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32(8):762–798

    Article  CAS  Google Scholar 

  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):169–188

    Article  CAS  Google Scholar 

  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):161–171

    Article  CAS  Google Scholar 

  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):415–426

    Article  CAS  Google Scholar 

  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):158–165

    Article  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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):1079–1091

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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):2408–2416

    Article  CAS  Google Scholar 

  16. Xu F, Neoh K, Kang E (2009) Bioactive surfaces and biomaterials via atom transfer radical polymerization. Prog Polym Sci 34(8):719–761

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  18. Lee AS, Gast AP, Bütün V, Armes SP (1999) Characterizing the structure of pH dependent polyelectrolyte block copolymer micelles. Macromolecules 32(13):4302–4310

    Article  CAS  Google Scholar 

  19. Baines F, Billingham N, Armes S (1996) Synthesis and solution properties of water-soluble hydrophilic-hydrophobic block copolymers. Macromolecules 29(10):3416–3420

    Article  CAS  Google Scholar 

  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):6121–6131

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  29. Deray G (2002) Amphotericin B nephrotoxicity. J Antimicrob Chemother 49(suppl 1):37–41

    Article  CAS  Google Scholar 

  30. Rao JP, Geckeler KE (2011) Polymer nanoparticles: preparation techniques and size-control parameters. Prog Polym Sci 36(7):887–913

    Article  CAS  Google Scholar 

  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):630–635

    Article  CAS  Google Scholar 

  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):179–186

    Article  CAS  Google Scholar 

  33. Motala-Timol S, Jhurry D (2007) Synthesis of PDMAEMA–PCL–PDMAEMA triblock copolymers. Eur Polym J 43(7):3042–3049

    Article  CAS  Google Scholar 

  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):3853–3863

    Article  CAS  Google Scholar 

  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):4818–4829

    Article  CAS  Google Scholar 

  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):5920–5926

    Article  CAS  Google Scholar 

  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

    Chapter  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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):1636–1644

    Article  CAS  Google Scholar 

  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):4343–4351

    Article  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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):28–36

    Article  CAS  Google Scholar 

Download references

Acknowledgment

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

Author information

Authors and Affiliations

  1. Departamento de Química, Pontificia Universidad Javeriana, Carrera 7 No. 40-62, Bogotá, DC, Colombia

    Ivonne L. Diaz

  2. Departamento de Química, Universidad Nacional de Colombia, Carrera 45 No. 26-85, edificio 451 of 449, Bogotá, DC, Colombia

    Leon D. Perez

Authors
  1. Ivonne L. Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leon D. Perez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leon D. Perez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diaz, I.L., Perez, L.D. Synthesis and micellization properties of triblock copolymers PDMAEMA-b-PCL-b-PDMAEMA and their applications in the fabrication of amphotericin B-loaded nanocontainers. Colloid Polym Sci 293, 913–923 (2015). https://doi.org/10.1007/s00396-014-3478-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00396-014-3478-3

Keywords

Search

Navigation