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Nanosized micelles self-assembled from amphiphilic poly(citric acid)–poly(ε-caprolactone)–poly(citric acid) copolymers

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Abstract

In this study, novel ABA-type amphiphilic copolymers consisting of poly(citric acid) (PCA) (A) as hydrophilic segment and poly(ε-caprolactone) (PCL) (B) as hydrophobic block were prepared by an approach in the following two steps: (1) ring-opening polymerization (ROP) of ε-caprolactone with 1,5-pentanediol initiator to obtain a hydroxyl telechelic PCL; (2) melt polycondensation reaction of hydroxyl telechelic PCL and citric acid molecules. The prepared copolymers are capable of self-assembling into nanosized micelles in aqueous solution. The influence of the copolymer composition on the micelle dimensions was investigated. The critical micellar concentration of the copolymers is in the range of 5–6.3 × 10−2 mg/mL which is determined by the fluorescence probe technique using pyrene. Also the results indicate that CMC of self assembled micelles is influenced by the hydrophilicity of PCA–PCL–PCA copolymers depending on the CA/CP ratio, and these micelles may find great potential as drug carriers in biomedical fields.

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References

  1. 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 109:169–188. doi:10.1016/j.jconrel.2005.09.034

    Article  CAS  Google Scholar 

  2. Lee ES, Na K, Bae YH (2005) Super pH-sensitive multifunctional polymeric micelle. Nano Lett 5:325–329. doi:10.1021/nl0479987

    Article  CAS  Google Scholar 

  3. Hruby M, Konak C, Ulbrich K (2005) Polymeric micellar pH-sensitive drug delivery system for doxorubicin. J Control Release 103:137–148. doi:10.1016/j.jconrel.2004.11.017

    Article  CAS  Google Scholar 

  4. Rapoport N (2007) Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Prog Polym Sci 32:962–990. doi:10.1016/j.progpolymsci.2007.05.009

    Article  CAS  Google Scholar 

  5. Owen SC, Chan DPY, Shoichet MS (2012) Polymeric micelle stability. Nano Today 7:53–65. doi:10.1016/j.nantod.2012.01.002

    Article  CAS  Google Scholar 

  6. Rijcken CJF, Soga O, Hennink WE, van Nostrum CF (2007) Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: an attractive tool for drug delivery. J Control Release 120:131–148. doi:10.1016/j.jconrel.2007.03.023

    Article  CAS  Google Scholar 

  7. Oberoi HS, Laquer FC, Marky LA, Kabanov AV, Bronich TK (2011) Core cross-linked block ionomer micelles as pH-responsive carriers for cis-diamminedichloroplatinum(II). J Controll Release 153:64–72. doi:10.1016/j.jconrel.2011.03.028

    Article  CAS  Google Scholar 

  8. Osada K, Christie RJ, Kataoka K (2009) Polymeric micelles from poly(ethylene glycol)–poly(amino acid) block copolymer for drug and gene delivery. J R Soc Interface 6:S325–S339. doi:10.1098/rsif.2008.0547.focus

    Article  CAS  Google Scholar 

  9. Quan CY, Wei H, Shi Y, Li ZY, Cheng SX, Zhang XZ, Zhuo RX (2011) Fabrication of multifunctional shell cross-linked micelles for targeting drug release. Colloid Polym Sci 289:667–675. doi:10.1007/s00396-010-2337-0

    Article  CAS  Google Scholar 

  10. Ai H, Flask C, Weinberg B, Shuai X, Pagel MD, Farrel D, Duerk J, Gao J (2005) Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes. Adv Mater 17:1949–1959. doi:10.1002/adma.200401904

    Article  CAS  Google Scholar 

  11. Chang YC, Chu IM (2008) Methoxy poly(ethylene glycol)-b-poly(valerolactone) diblock polymeric micelles for enhanced encapsulation and protection of camptothecin. Eur Polym J 44:3922–3930. doi:10.1016/j.eurpolymj.2008.09.021

    Article  CAS  Google Scholar 

  12. Gong J, Chen M, Zheng Y, Wang S, Wang Y (2012) Polymeric micelles drug delivery system in oncology. J Control Release 149:312–323. doi:10.1016/j.jconrel.2011.12.012

    Article  Google Scholar 

  13. Zhu W, Li Y, Liu L, Zhang W, Chen Y, Xi F (2011) Biamphiphilic triblock copolymer micelles as a multifunctional platform for anticancer drug delivery. J Biomed Mater Res 96A:330–340. doi:10.1002/jbm.a.32985

    Article  CAS  Google Scholar 

  14. Li W, Nakayama M, Akimoto J, Okano T (2011) Effect of block compositions of amphiphilic block copolymers on the physicochemical properties of polymeric micelles. Polymer 52:3783–3790. doi:10.1016/j.polymer.2011.06.026

    Article  CAS  Google Scholar 

  15. Soo PL, Luo L, Maysinger D, Eisenberg A (2002) Incorporation and release of hydrophobic probes in biocompatible polycaprolactone-block-poly(ethylene oxide) micelles: implications for drug delivery. Langmuir 18:9996–10004. doi:10.1021/la026339b

    Article  CAS  Google Scholar 

  16. Mondon K, Zeisser-Labouèbe M, Gurny R, Moller M (2011) Novel cyclosporin A formulations using MPEG-hexyl-substituted polylactide micelles: a suitability study. Eur J Pharm Biopharm 77:56–65. doi:10.1016/j.ejpb.2010.09.012

    Article  CAS  Google Scholar 

  17. Xu B, Yuan J, Ding T, Gao Q (2010) Amphiphilic biodegradable poly(e-caprolactone)–poly(ethylene glycol)–poly(e-caprolactone) triblock copolymers: synthesis, characterization and their use as drug carriers for folic acid. Polym Bull 64:537–551. doi:10.1007/s00289-009-0157-5

    Article  CAS  Google Scholar 

  18. Wang T, Li M, Gao H, Wu Y (2011) Nanoparticle carriers based on copolymers of poly(e-caprolactone) and hyperbranched polymers for drug delivery. J Colloid Interface Sci 353:107–115. doi:10.1016/j.jcis.2010.09.053

    Article  CAS  Google Scholar 

  19. Carstens MG, van Nostrum CF, Verrijk R, De Leede LGJ, Crommelin DJA, Hennink WE (2008) A mechanistic study on the chemical and enzymatic degradation of PEG-oligo(e-caprolactone) micelles. J Pharm Sci 97:506–518. doi:10.1002/jps.21092

    Article  CAS  Google Scholar 

  20. Tyrrell ZL, Shen Y, Radosz M (2010) Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers. Prog Polym Sci 35:1128–1143. doi:10.1016/j.progpolymsci.2010.06.003

    Article  CAS  Google Scholar 

  21. Deng M, Wang R, Rong G, Sun J, Zhang X, Chen X, Jing X (2004) Synthesis of a novel structural triblock copolymer of poly(g-benzyl-l-glutamic acid)-b-poly(ethylene oxide)-b-poly(e-caprolactone). Biomaterials 25:3553–3558. doi:10.1016/j.biomaterials.2003.10.018

    Article  CAS  Google Scholar 

  22. Tian H, Tang Z, Zhuang X, Chen X, Jing X (2012) Biodegradable synthetic polymers: preparation, functionalization and biomedical application. Prog Polym Sci 37:237–280. doi:10.1016/j.progpolymsci.2011.06.004

    Article  CAS  Google Scholar 

  23. Dai W, Zhang Y, Du Z, Ru M, Lang M (2010) The pH-induced thermosensitive poly (NIPAAm-co-AAc-co-HEMA)-g-PCL micelles used as a drug carrier. J Mater Sci Mater Med 21:1881–1890. doi:10.1007/s10856-010-4049-x

    Article  CAS  Google Scholar 

  24. Sun TM, Du JZ, Yan LF, Mao HQ, Wang J (2008) Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery. Biomaterials 29:4348–4355. doi:10.1016/j.biomaterials.2008.07.036

    Article  CAS  Google Scholar 

  25. Qiua LY, Bae YH (2007) Self-assembled polyethylenimine-graft-poly(ε-caprolactone) micelles as potential dual carriers of genes and anticancer drugs. Biomaterials 28:4132–4142. doi:10.1016/j.biomaterials.2007.05.035

    Article  Google Scholar 

  26. Lin D, Huang Y, Jiang Q, Zhang W, Yue X, Guo S, Xiao P, Du Q, Xing J, Deng L, Liang Z, Dong A (2011) Structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles in siRNA delivery. Biomaterials 32:8730–8742. doi:10.1016/j.biomaterials.2011.07.089

    Article  CAS  Google Scholar 

  27. Qiu F, Feng J, Wu DQ, Zhang XZ, Zhuo RX (2009) Nanosized micelles self-assembled from amphiphilic dextran-graft-methoxypolyethylene glycol/poly(e-caprolactone) copolymers. Eur Polym J 45:1024–1031. doi:10.1016/j.eurpolymj.2008.12.025

    Article  CAS  Google Scholar 

  28. Naeini AT, Adeli M, Vossoughi M (2010) Poly(citric acid)-block-poly(ethylene glycol) copolymers-new biocompatible hybrid materials for nanomedicine. Nanomedicine 6:556–562. doi:10.1016/j.nano.2009.11.008

    Article  CAS  Google Scholar 

  29. Yang J, Webb AR, Ameer GA (2004) Novel citric acid based biodegradable elastomers for tissue engineering. Adv Mater 16:511–516. doi:10.1002/adma.200306156

    Article  CAS  Google Scholar 

  30. Zou T, Cheng SX, Zhang XZ, Zhuo RZ (2007) Novel cholic acid functionalized star oligo/poly(dl-lactide)s for biomedical applications. J Biomed Mater Res B 82:400–407. doi:10.1002/jbm.b.30745

    Google Scholar 

  31. Yang J, Webb AR, Pickerill SJ, Hageman G, Ameer GA (2006) Synthesis and evaluation of poly(diol citrate) biodegradable elastomers. Biomaterials 27:1889–1898. doi:10.1016/j.biomaterials.2005.05.106

    Article  CAS  Google Scholar 

  32. Turunen MPK, Laurila T, Kivilahti JK (2006) Reactive blending approach to modify spin-coated epoxy film: part I. Synthesis and characterization of star-shaped poly(ε-caprolactone). J Appl Polym Sci 101:3677–3688. doi:10.1002/app.22832

    Article  CAS  Google Scholar 

  33. Yao F, Bai Y, Chen W, An X, Yao K, Sun P, Lin H (2004) Synthesis and characterization of functional l-lactic acid/citric acid oligomer. Eur Polym J 40:1895–1901. doi:10.1016/j.eurpolymj.2004.04.017

    Article  CAS  Google Scholar 

  34. Lee J, Cho EC, Cho K (2004) Incorporation and release behavior of hydrophobic drug in functionalized poly(d,l-lactide)-block-poly(ethylene oxide) micelles. J Controll Release 94:323–335. doi:10.1016/j.jconrel.2003.10.012

    Article  CAS  Google Scholar 

  35. Ma Y, Huang L, Song C, Zeng X, Liu G, Mei L (2010) Nanoparticle formulation of poly(ε-caprolactone-co-lactide)-d-α-tocopheryl polyethylene glycol 1000 succinate random copolymer for cervical cancer treatment. Polymer 51:5952–5959. doi:10.1016/j.polymer.2010.10.029

    Article  CAS  Google Scholar 

  36. Sha K, Li D, Li Y, Liu X, Wang S, Guan J, Wang J (2007) Synthesis, characterization, and micellization of an epoxy-based amphiphilic diblock copolymer of e-caprolactone and glycidyl methacrylate by enzymatic ring-opening polymerization and atom transfer radical polymerization. J Polym Sci: Part A: Pol Chem 45:5037–5049. doi:10.1002/pola.22000

    Article  CAS  Google Scholar 

  37. Benahmed A, Ranger M, Leroux JC (2001) Novel polymeric micelles based on the amphiphilic diblock copolymer poly(n-vinyl-2-pyrrolidone)-block-poly(d,l-lactide). Pharm Res 18:323–328

    Article  CAS  Google Scholar 

  38. Bian Q, Xiao Y, Lang M (2012) Thermoresponsive biotinylated star amphiphilic block copolymer: synthesis, self-assembly, and specific target recognition. Polymer 53:1684–1693. doi:10.1016/j.polymer.2012.02.031

    Article  CAS  Google Scholar 

  39. Luo L, Ranger M, Lessard DG, Le Garrec D, Gori S, Leroux JC, Rimmer S, Smith D (2004) Novel amphiphilic diblock copolymer of low molecular weight poly(N-vinylpyrrolidone)-block-poly(d,l-lactide): synthesis, characterization, and micellization. Macromolecules 37:4008–4013. doi:10.1021/ma035910q

    Article  CAS  Google Scholar 

  40. Yang L, Zhao Z, Wei J, El Ghzaoui A, Li S (2007) Micelles formed by self-assembling of polylactide/poly(ethylene glycol) block copolymers in aqueous solutions. J Colloid Interface Sci 314:470–477. doi:10.1016/j.jcis.2007.05.074

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Industrial Connection Office of University of Tabriz. The authors were grateful to Dr. Mohsen Adeli for his efficient collaborations.

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  1. Laboratory of Polymer, Faculty of Chemistry, University of Tabriz, P.O. Box 5166616471, Tabriz, Iran

    Homa Gheybi & Ali Akbar Entezami

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  1. Homa Gheybi
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Correspondence to Ali Akbar Entezami.

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Gheybi, H., Entezami, A.A. Nanosized micelles self-assembled from amphiphilic poly(citric acid)–poly(ε-caprolactone)–poly(citric acid) copolymers. Polym. Bull. 70, 1875–1894 (2013). https://doi.org/10.1007/s00289-012-0885-9

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  • DOI: https://doi.org/10.1007/s00289-012-0885-9

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