Controlling antibiotic release from mesoporous silica nano drug carriers via self-assembled polyelectrolyte coating

  • Tasnuva Tamanna
  • Jurgen B. Bulitta
  • Aimin YuEmail author
Delivery Systems
Part of the following topical collections:
  1. Delivery Systems


Mesoporous silica nanoparticles (MSNs) have been explored as controlled drug delivery systems since the early 2000s, but many fundamental questions remain for this important application. We sought to design a pH controlled delivery system of gentamicin, an aminoglycoside antibiotic, based on MSNs. Under optimal conditions, MSN was able to load 219 µg gentamicin per mg MSNs. Polymeric networks encompassing gentamicin loaded MSNs were then established to tune the release kinetics. Embedding of drug pre-loaded MSNs was performed by an efficient layer-by-layer (LbL) self-assemble strategy using polystyrene sulfonate (PSS) and poly (allylamine hydrochloride) (PAH). We characterised the release kinetics by nonlinear mixed-effects modelling in the S-ADAPT software. The mean release time from uncoated MSNs was 3.6 days at pH 7.4 and 0.4 days at pH 1.4. A further slower release was achieved by diffusion through one or two PSS/PAH bilayer(s) which had a mean transit time of 6.0 days at pH 7.4 and 3.5 days at pH 1.4. The number of bilayers affected the shape of the release profile. The developed nano-drug carriers combined with the self-assembled polyelectrolyte coating allowed us to tune the release kinetics by pH and the number of bilayers.


Drug Release Gentamicin Simulated Body Fluid Drug Loading Release Kinetic 
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.



J. B. B. acknowledged the Australian Research Council for his DECRA Fellowship (DE120103084).


  1. 1.
    Carbone C, Campisi A, Musumeci T, Raciti G, Bonfanti R, Puglisi G. FA-loaded lipid drug delivery systems: preparation, characterization and biological studies. Eur J Pharm Sci. 2014;52(1):12–20.CrossRefGoogle Scholar
  2. 2.
    Ariga K, Ji Q, McShane MJ, Lvov YM, Vinu A, Hill JP. Inorganic nanoarchitectonics for biological applications. Chem Mater. 2012;24(5):728–37.CrossRefGoogle Scholar
  3. 3.
    Hasan AS, Socha M, Lamprecht A, Ghazouani FE, Sapin A, Hoffman M, et al. Effect of the microencapsulation of nanoparticles on the reduction of burst release. Int J Pharm. 2007;344(1–2):53–61.CrossRefGoogle Scholar
  4. 4.
    Patel BK, Parikh RH, Aboti PS. Development of oral sustained release rifampicin loaded chitosan nanoparticles by design of experiment. J Drug Deliv. 2013;2013:370938.CrossRefGoogle Scholar
  5. 5.
    Zhang L, Pornpattananangkul D, Hu CMJ, Huang CM. Development of nanoparticles for antimicrobial drug delivery. Curr Med Chem. 2010;17(6):585–94.CrossRefGoogle Scholar
  6. 6.
    Kwon S, Singh RK, Perez RA, Abou Neel EA, Kim H-W, Chrzanowski W. Silica-based mesoporous nanoparticles for controlled drug delivery. J Tissue Eng. 2013;4(1):1–18.Google Scholar
  7. 7.
    Vallet-Regí M, Balas F, Arcos D. Mesoporous materials for drug delivery. Angew Chem Int Ed. 2007;46(40):7548–58.CrossRefGoogle Scholar
  8. 8.
    Trewyn BG, Slowing II, Giri S, Chen HT, Lin VSY. Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol-gel process and applications in controlled release. Acc Chem Res. 2007;40(9):846–53.CrossRefGoogle Scholar
  9. 9.
    Xu W, Gao Q, Xu Y, Wu D, Sun Y, Shen W, et al. Controllable release of ibuprofen from size-adjustable and surface hydrophobic mesoporous silica spheres. Powder Technol. 2009;191(1–2):13–20.CrossRefGoogle Scholar
  10. 10.
    Izquierdo-Barba I, Colilla M, Vallet-Regi M. Nanostructured mesoporous silicas for bone tissue regeneration. J Nanomater. 2008;2008:106970.CrossRefGoogle Scholar
  11. 11.
    Strømme M, Brohede U, Atluri R, Garcia-Bennett AE. Mesoporous silica-based nanomaterials for drug delivery: evaluation of structural properties associated with release rate. Wiley Interdiscip Rev. 2009;1(1):140–8.Google Scholar
  12. 12.
    Sun JT, Hong CY, Pan CY. Fabrication of PDEAEMA-coated mesoporous silica nanoparticles and pH-responsive controlled release. J Phys Chem C. 2010;114(29):12481–6.CrossRefGoogle Scholar
  13. 13.
    Hu X, Wang Y, Peng B. Chitosan-capped mesoporous silica nanoparticles as pH-responsive nanocarriers for controlled drug release. Chem Asian J. 2014;9(1):319–27.CrossRefGoogle Scholar
  14. 14.
    Yanes RE, Tamanoi F. Development of mesoporous silica nanomaterials as a vehicle for anticancer drug delivery. Therapeutic Deliv. 2012;3(3):389–404.CrossRefGoogle Scholar
  15. 15.
    Chen Z, Li Z, Lin Y, Yin M, Ren J, Qu X. Bioresponsive hyaluronic acid-capped mesoporous silica nanoparticles for targeted drug delivery. Chemistry. 2013;19(5):1778–83.CrossRefGoogle Scholar
  16. 16.
    Nadrah P, Maver U, Jemec A, Tišler T, Bele M, Dražić G, et al. Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica. ACS Appl Mater Interfaces. 2013;5(9):3908–15.CrossRefGoogle Scholar
  17. 17.
    Yan H, Teh C, Sreejith S, Zhu L, Kwok A, Fang W, et al. Functional mesoporous silica nanoparticles for photothermal-controlled drug delivery in vivo. Angew Chem Int Ed. 2012;51(33):8373–7.CrossRefGoogle Scholar
  18. 18.
    Aznar E, Mondragõn L, Ros-Lis JV, Sancenõn F, Marcos MD, Martínez-Máñez R, et al. Finely tuned temperature-controlled cargo release using paraffin-capped mesoporous silica nanoparticles. Angew Chem Int Ed. 2011;50(47):11172–5.CrossRefGoogle Scholar
  19. 19.
    Liu R, Liao P, Liu J, Feng P. Responsive polymer-coated mesoporous silica as a pH-sensitive nanocarrier for controlled release. Langmuir. 2011;27(6):3095–9.CrossRefGoogle Scholar
  20. 20.
    Popat A, Liu J, Lu GQ, Qiao SZ. A pH-responsive drug delivery system based on chitosan coated mesoporous silica nanoparticles. J Mater Chem. 2012;22(22):11173–8.CrossRefGoogle Scholar
  21. 21.
    Donlan RM. Biofilms and device-associated infections. Emerg Infect Dis. 2001;7(2):277.CrossRefGoogle Scholar
  22. 22.
    Marques MR, Loebenberg R, Almukainzi M. Simulated biological fluids with possible application in dissolution testing. Dissolution Technol. 2011;18(3):15–28.CrossRefGoogle Scholar
  23. 23.
    Kim TW, Chung PW, Lin VSY. Facile synthesis of monodisperse spherical MCM-48 mesoporous silica nanoparticles with controlled particle size. Chem Mater. 2010;22(17):5093–104.CrossRefGoogle Scholar
  24. 24.
    Bauer RJ, Guzy S, Ng C. A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples. AAPS J. 2007;9(1):7.CrossRefGoogle Scholar
  25. 25.
    Bulitta JB, Bingölbali A, Shin BS, Landersdorfer CB. Development of a new pre-and post-processing tool (SADAPT-TRAN) for nonlinear mixed-effects modeling in S-ADAPT. AAPS J. 2011;13(2):201–11.CrossRefGoogle Scholar
  26. 26.
    Bulitta JB, Landersdorfer CB. Performance and robustness of the Monte Carlo importance sampling algorithm using parallelized S-ADAPT for basic and complex mechanistic models. AAPS J. 2011;13(2):212–26.CrossRefGoogle Scholar
  27. 27.
    Liu Y, Tourbin M, Lachaize S, Guiraud P. Silica nanoparticle separation from water by aggregation with AlCl3. Ind Eng Chem Res. 2011;51(4):1853–63.CrossRefGoogle Scholar
  28. 28.
    Schwarz S, Lunkwitz K, Keßler B, Spiegler U, Killmann E, Jaeger W. Adsorption and stability of colloidal silica. Colloids Surf A. 2000;163(1):17–27.CrossRefGoogle Scholar
  29. 29.
    Lee HY, Choi KH, Bank N. Protective effect of urinary alkalinization on gentamicin nephrotoxicity in rats. Yonsei Med J. 1988;29(3):225–32.CrossRefGoogle Scholar
  30. 30.
    Zhu YF, Shi JL, Li YS, Chen HR, Shen WH, Dong XP. Hollow mesoporous spheres with cubic pore network as a potential carrier for drug storage and its in vitro release kinetics. J Mater Res. 2005;20(1):54–61.CrossRefGoogle Scholar
  31. 31.
    Abdelghany SM, Quinn DJ, Ingram RJ, Gilmore BF, Donnelly RF, Taggart CC, et al. Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection. Int J Nanomed. 2012;7:4053–63.Google Scholar
  32. 32.
    Lewis SR, Datta S, Gui M, Coker EL, Huggins FE, Daunert S, et al. Reactive nanostructured membranes for water purification. Proc Natl Acad Sci. 2011;108(21):8577–82.CrossRefGoogle Scholar
  33. 33.
    De Geest BG, Sanders NN, Sukhorukov GB, Demeester J, De Smedt SC. Release mechanisms for polyelectrolyte capsules. Chem Soc Rev. 2007;36(4):636–49.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Faculty of Science, Engineering and TechnologySwinburne University of TechnologyMelbourneAustralia
  2. 2.Faculty of Pharmacy and Pharmaceutical SciencesMonash UniversityMelbourneAustralia

Personalised recommendations