Advertisement

Journal of Materials Science

, Volume 49, Issue 3, pp 1437–1447 | Cite as

Polyethyleneimine-functionalized large pore ordered silica materials for poorly water-soluble drug delivery

  • A. Martín
  • R. A. García
  • D. Sen Karaman
  • J. M. Rosenholm
Article

Abstract

Four ordered mesoporous silica supports with different pore structure characteristics were investigated for their drug loading and release abilities with regard to their structural variabilities as well as implications of surface modification. The (model) drug molecule in question was the poorly water-soluble glucocorticoid Prednisolone, composed of a steroid skeleton with functional groups in the form of carbonyls and hydroxyls. Under non-aqueous conditions, such as those applied for drug loading, these functional groups are expected to interact with the surface silanols of the silica supports, but this interaction could possibly also be enhanced by introducing amino groups to the silica surfaces. Thus, all four supports were further functionalized by surface hyperbranching of polyethyleneimine), PEI, which was successfully incorporated to all supports in high amounts (>30 wt%). However, the accessibility of the pore system after organic modification was dependent on the pore sizes and structures, highlighting the importance of using large-pore mesophases with adequate structures when aiming for applications involving (bulky) guest molecules. Additionally, after incorporation of large amounts of guest molecules (40 wt%), full water accessibility was retained in that the loaded cargo could be rapidly released from the carrier matrixes, which is a crucial requirement when formulating poorly soluble substances. Results displayed that the release of Prednisolone from the silica supports occurred faster than the dissolution of the pure drug. All silica materials released more than 85 % of the adsorbed drug in 5 h, independently of the support material. Thus, the confinement of Prednisolone inside the mesopores seems to be the main reason for the faster kinetic release rate. These constraints imply that Prednisolone becomes more mobile inside the pores, and therefore more soluble in release medium. These results confirm the potential of silica supports as drug delivery carriers for drugs with limited water solubility such as steroids.

Keywords

Mesoporous Silica Pure Silica Silica Material Aziridine Polyethyleneimine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The financial support by Ministerio de Ciencia e Innovación of Spain, through the Project CTQ2011-22707, is gratefully acknowledged. A. Martín thanks the Rey Juan Carlos University for the grant “Ayudas a la Movilidad: Estancias Breves de Investigación del Programa Propio de Fomento y Desarrollo de la Investigación.” The Academy of Finland projects #137101, 140193, 260599 (J.M.R), Centre of Excellence for Functional Materials (D.S.K.) are gratefully acknowledged for financial support.

References

  1. 1.
    Rosenholm JM, Lindén M (2008) Towards establishing structure–activity relationships for mesoporous silica in drug delivery applications. J Control Release 128(2):157–164PubMedCrossRefGoogle Scholar
  2. 2.
    Manzano M, Vallet-Regí M (2010) New developments in ordered mesoporous materials for drug delivery. J Mater Chem 20:5593–5604CrossRefGoogle Scholar
  3. 3.
    Munoz B, Ramila A, Perez-Pariente J, Diaz I, Vallet-Regí M (2003) MCM-41 organic modification as drug delivery rate regulator. Chem Mater 15:500–503CrossRefGoogle Scholar
  4. 4.
    Zeng W, Qian XF, Zhang YB, Yin J, Zhu ZK (2005) Organic modified mesoporous MCM-41 through solvothermal process as drug delivery system. Mater Res Bull 40:766–772CrossRefGoogle Scholar
  5. 5.
    Balas F, Manzano M, Horcajada P, Vallet-Regí M (2006) Confinement and Controlled Release of Bisphosphonates on Ordered Mesoporous Silica-Based Materials. J Am Chem Soc 128:8116–8117PubMedCrossRefGoogle Scholar
  6. 6.
    Vallet-Regí M, Balas F, Colilla M, Manzano M (2008) Bone-regenerative bioceramic implants with drug and protein controlled delivery capability. Prog Solid State Chem 36:163–191CrossRefGoogle Scholar
  7. 7.
    Lai CY, Trewyn BG, Jeftinija DM, Jeftinija K, Xu S, Jeftinija S, Lin VS (2003) A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules. J Am Chem Soc 125:4451–4459PubMedCrossRefGoogle Scholar
  8. 8.
    Maria Chong AS, Zhao XS (2003) Functionalization of SBA-15 with APTES and characterization of functionalized materials. J Phys Chem B 107(46):12650–12657CrossRefGoogle Scholar
  9. 9.
    Hall SR, Fowler CE, Mann S, Lebeau B (1999) Template-directed synthesis of bi-functionalized organo-MCM-41 and phenyl-MCM-48 silica mesophases. Chem Commun 201–202Google Scholar
  10. 10.
    Yokoi T, Yoshitake H, Tatsumi T (2004) Synthesis of amino-functionalized MCM-41 via direct co-condensation and post-synthesis grafting methods using mono-, di- and tri-amino-organoalkoxysilanes. J Mater Chem 14:951–957CrossRefGoogle Scholar
  11. 11.
    Szegedi A, Popova M, Goshev I, Mihály J (2001) Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release. J Solid State Chem 184:1201–1207CrossRefADSGoogle Scholar
  12. 12.
    Lim MH, Stein A (1999) Comparative studies of grafting and direct syntheses of inorganic−organic hybrid mesoporous materials. Chem Mater 11:3285–3295CrossRefGoogle Scholar
  13. 13.
    García N, Benito E, Guzmán J, Tiemblo P, Morales V, García RA (2007) Functionalization of SBA-15 by an acid-actalyzed approach: A surface characterization study. Microporous Mesoporous Mater 106:129–139CrossRefGoogle Scholar
  14. 14.
    Hoffmann F, Cornelius M, Morell J, Froba M (2006) Silica-based mesoporous organic-inorganic hybrid materials. Angew Chem Int Ed 45:3216–3251CrossRefGoogle Scholar
  15. 15.
    Kim CO, Cho SJ, Park JW (2003) Hyperbranching polymerization of aziridine on silica solid substrates leading to a surface of highly dense reactive amine groups. J Colloid Interface Sci 260(2):374–378PubMedCrossRefGoogle Scholar
  16. 16.
    Rosenholm JM, Penninkangas A, Lindén M (2006) Amino-functionalization of large-pore mesoscopically ordered silica by a one-step hyperbranching polymerization of a surface-grown polyethyleneimine. Chem Commun 3909–3911Google Scholar
  17. 17.
    Rosenholm JM, Lindén M (2007) Wet-chemical Analysis of Surface Concentration of Accessible Groups on Different Amino-Functionalized Mesoporous SBA-15 Silicas. Chem Mater 19(20):5023–5034CrossRefGoogle Scholar
  18. 18.
    Martín A, Morales G, Martínez F, van Grieken R, Cao L, Kruk M (2010) Acid hybrid catalysts from poly(styrenesulfonic acid) grafted onto ultra-large-pore SBA-15 silica using atom transfer radical polymerization. J Mater Chem 20:8026–8035CrossRefGoogle Scholar
  19. 19.
    Blin JL, Su BL (2002) Tailoring pore size of ordered mesoporous silicas using one or two organic auxiliaries as expanders. Langmuir 18(13):5303–5308CrossRefGoogle Scholar
  20. 20.
    Kruk M, Cao L (2007) Pore size tailoring in large-pore SBA-15 silica synthesized in the presence of hexane. Langmuir 23:7247–7254PubMedCrossRefGoogle Scholar
  21. 21.
    Cao L, Kruk M (2010) Synthesis of large-pore SBA-15 silica from tetramethyl orthosilicate using triisopropylbenzene as micelle expander. Colloids Surf A 357:91–96CrossRefGoogle Scholar
  22. 22.
    Fulvio PF, Pikus S, Jaroniec M (2005) Tailoring properties of SBA-15 materials by controlling conditions of hydrothermal synthesis. J Mater Chem 15:5049–5053CrossRefGoogle Scholar
  23. 23.
    Sun J, Zhang H, Ding M, Chen Y, Bao X, Klein-Hoffman A, Pfänder N, Su DS (2005) Alkanes-assisted low temperature formation of highly ordered SBA-15 with large cylindrical mesopores. Chem Commun 5343–5345Google Scholar
  24. 24.
    Zhang H, Sun J, Ma D, Weinberg G, Su DS, Bao X (2006) Engineered complex emulsion system: Toward modulation the pore length and morphological architecture of mesoporous silica. J Phys Chem B 110:25908–25915PubMedCrossRefGoogle Scholar
  25. 25.
    Kang K, Rhee H (2005) Synthesis and characterization of novel mesoporous silica with large wormhole-like pores: Use of TBOS as silicon source. Microporous Mesoporous Mater 84:34–40CrossRefGoogle Scholar
  26. 26.
    Tamanoi F, Lu J, Liong M, Zink JI (2007) Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs. Small 3(8):1341–1346PubMedCrossRefGoogle Scholar
  27. 27.
    Nishiwaki A, Watanable A, Higashi K, Tozuka Y, Moribe K, Yamamoto K (2009) Molecular states of prednisolone dispersed in folded sheet mesoporous silica (FSM-16). Int J Pharm 378:17–22PubMedCrossRefGoogle Scholar
  28. 28.
    Sagcal-Gironella ACP, Sherwin CMT, Tirona RG, Rieder MJ, Brunner HI, Vinks AA (2011) Pharmacokinetics of prednisolone at steady state in young patients with systemic lupus erythematosus on prednisone therapy: an open-label, single-dose study. Clin Therapeutics 33(10):1524–1536CrossRefGoogle Scholar
  29. 29.
    Izquierdo-Barba I, Martinez A, Doadrio AL, Perez-Pariente J, Vallet-Regí M (2005) Release evaluation of drugs from ordered three-dimensional silica structures. Eur J Pharm Sci 26:365–373PubMedCrossRefGoogle Scholar
  30. 30.
    Song SW, Hidajat K, Kawi S (2005) Functionalized SBA-15 materials as carriers for controlled drug delivery: influence of surface properties on matrix−drug interactions. Langmuir 21:9568–9575PubMedCrossRefGoogle Scholar
  31. 31.
    Heikkila T, Salonen J, Tuura J, Hamdy MS, Mul G, Kumar N, Salmi T, Murzin DY, Laitinen L, Kaukonen AM, Hirvonen J, Lehto VP (2007) Mesoporous silica material TUD-1 as a drug delivery system. Int J Pharm 331:133–138PubMedCrossRefGoogle Scholar
  32. 32.
    Vivero-Escoto JL, Slowing II, Wu CW, Lin VSY (2009) Photoinduced intracellular controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere. J Am Chem Soc 131:3462–3463PubMedCrossRefGoogle Scholar
  33. 33.
    Bhirde AA, Patel V, Gavard J, Zhang G, Sousa AA, Masedunskas A, Leapman RD, Weigert R, Gutkind JS, Rusling JF (2009) Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. ACS Nano 3(2):307–316PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Rosenholm JM, Sahlgren C, Lindén M (2011) Multifunctional mesoporous silica nanoparticles for combined therapeutic, diagnostic and targeted action in cancer treatment. Curr Drug Targets 12:1166–1186PubMedCrossRefGoogle Scholar
  35. 35.
    Zhao D, Feng J, Huo Q, Melosh N, Fredrikson GH, Chmelka BF, Stucky GD (1998) Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores. Science 279:548–552PubMedCrossRefADSGoogle Scholar
  36. 36.
    Huo Q, Margolese DI, Stucky GD (1996) Surfactant control of phases in the synthesis of mesoporous silica-based materials. Chem Mater 8:1147–1160CrossRefGoogle Scholar
  37. 37.
    Kruk M, Hui CM (2008) Synthesis and characterization of large-pore FDU-12 silica. Microporous Mesoporous Mater 114:64–73CrossRefGoogle Scholar
  38. 38.
    Kumar D, Schumacher K, von du Fresne Hohenesche C, Grun M, Unger KK (2001) MCM-41, MCM-48 and related mesoporous adsorbents: their synthesis and characterization. Colloids Surf A 187:109–116CrossRefGoogle Scholar
  39. 39.
    Jung HS, SikMoon D, Lee JK (2012) Quantitative analysis and efficient surface modification of silica nanoparticles. J Nanomater 1–8Google Scholar
  40. 40.
    Rouquerol F, Rouquerol J, Sing K (1999) Adsorption by powders and porous solids. Academic Press, LondonCrossRefGoogle Scholar
  41. 41.
    Cao L, Man T, Kruk M (2009) Synthesis of ultra-large-pore SBA-15 silica with two-dimensional hexagonal structure using triisopropylbenzene as micelle expander. Chem Mater 21:1144–1153CrossRefGoogle Scholar
  42. 42.
    Anbia M, Salehi S (2012) Removal of acid dyes from aqueous media by adsorption onto amino-functionalized nanoporous silica SBA-3. Dyes Pigm 94:1–9CrossRefGoogle Scholar
  43. 43.
    Goltner CG, Smarsly B, Berton B, Atonietti M (2001) On the microporous nature of mesoporous molecular sieves. Chem Mater 13:1617–1624CrossRefGoogle Scholar
  44. 44.
    Calleja G, Sanz R, Arencibia A, Sanz-Pérez ES (2011) Influence of Drying Conditions on Amine-Functionalized SBA-15 as Adsorbent of CO2. Top Catal 54:135–145CrossRefGoogle Scholar
  45. 45.
    Pang J, Zhao L, Zhang L, Li Z, Luan Y (2013) Folate-conjugated hybrid SBA-15 particles for targeted anticancer drug delivery. J Colloid Interface Sci 395:31–39PubMedCrossRefGoogle Scholar
  46. 46.
    Charnay C, Bégu S, Tourné-Péteilh C, Nicole L, Lerner DA, Devoisselle JM (2004) Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property. Eur J Pharm Sci 57:533–540Google Scholar
  47. 47.
    Hata H, Saeki S, Kimura T, Sugahara Y, Kuroda K (1999) Adsorption of taxol into ordered mesoporous silicas with various pore diameters. Chem Mater 11:1110–1119CrossRefGoogle Scholar
  48. 48.
    Kirkland JJ (1971) Modern practice of liquid chromatography. Wiley, New YorkGoogle Scholar
  49. 49.
    Hildebrand JH (1936) The solubility of non-electrolytes. Reinhold, New YorkGoogle Scholar
  50. 50.
    Hansen CM (1967) The three dimensional solubility parameter—key to paint component affinities II. J Paint Technol 39:505–510Google Scholar
  51. 51.
    Xu W, Riikonen J, Lehto VP (2012) Mesoporous systems for poorly soluble drugs. Int J Pharmaceut 453:181–197CrossRefGoogle Scholar
  52. 52.
    Andersson J, Rosenholm J, Areva S, Lindén M (2004) Influences of material characteristics on ibuprofen drug loading and release profiles from ordered micro- and mesoporous silica matrices. Chem Mater 16:4160–4167CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • A. Martín
    • 1
  • R. A. García
    • 1
  • D. Sen Karaman
    • 2
  • J. M. Rosenholm
    • 2
  1. 1.Department of Chemical and Environmental TechnologyUniversidad Rey Juan CarlosMóstoles, MadridSpain
  2. 2.Center for Functional Materials Laboratory for Physical ChemistryÅbo Akademi UniversityTurkuFinland

Personalised recommendations