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Silica nanoparticle synthesis by experimental design for drug and gene delivery applications

Yıl 2023, Cilt: 27 Sayı: 1, 12 - 22, 28.06.2025

Gözde Ultav Hayrettin Tonbul , Adem Şahin , Yılmaz Çapan

Öz

Silica nanoparticles (SNPs) are one of the most researched drug/gene delivery platforms due to their easy and cheap production. Their toxicity depends on the nanoparticle characteristics like particle size or shape. It is well known that the smaller nanoparticles have a better cellular uptake potential. For this reason, in this study, we synthesized SNPs with a particle size of around 100 nm via an experimental design method that combines Technique for Order Preference by Similarity to the Ideal Solution (TOPSIS) with Taguchi design to optimize more than one response. After the optimization, average particle size, particle size distribution, zeta potential, and particle morphology of validated SNPs were analyzed. The cytotoxicity studies were performed on fibroblast cells (L929) for 48 and 72 hours. Results show that obtained nanoparticles were spherical-shaped with a size of around 100 nm and had good biocompatibility.

Anahtar Kelimeler

TOPSIS based Taguchi Design design of experiment silica nanoparticles drug delivery gene delivery

Kaynakça

  • [1] Akhter, F., Rao, A.A., Abbasi, M.N. et al. A Comprehensive Review of Synthesis, Applications and Future Prospects for Silica Nanoparticles (SNPs). Silicon, 2022. [CrossRef]
  • [2] Stöber, W., A. Fink, and E. Bohn, Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science, 1968. 26(1): 62-69. [CrossRef]
  • [3] Rahman, I.A. and V. Padavettan, Synthesis of Silica Nanoparticles by Sol-Gel: Size-Dependent Properties, Surface Modification, and Applications in Silica-Polymer Nanocomposites—A Review. Journal of Nanomaterials, 2012. [CrossRef]
  • [4] Bhakta, G., et al., Multifunctional silica nanoparticles with potentials of imaging and gene delivery. Nanomedicine: Nanotechnology, Biology and Medicine, 2011. 7(4): 472-479. [CrossRef]
  • [5] M. Ways, T.M.; Ng, K.W.; Lau, W.M.; Khutoryanskiy, V.V. Silica Nanoparticles in Transmucosal Drug Delivery. Pharmaceutics, 2020. 12(8): 751-775. [CrossRef]
  • [6] Prabha, S., et al., Effect of size on biological properties of nanoparticles employed in gene delivery. Artificial Cells, Nanomedicine, and Biotechnology, 2016. 44(1): 83-9110. [CrossRef]
  • [7] Sahin, A., et al., A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles’ characteristics and efficacy of intracellular delivery. Artificial Cells, Nanomedicine, and Biotechnology, 2017. 45(8): 1657-1664. [CrossRef]
  • [8] Kumar Khanna, V., Targeted delivery of nanomedicines. ISRN pharmacology, 2012. 2012: 571394-571394. [CrossRef]
  • [9] Phadke, M.S., Quality Engineering Using Robust Design, PTR Prentice-Hall. Inc., Englewood Cliffs, NJ, 1989
  • [10] Davis, R. , John, P. . Application of Taguchi-Based Design of Experiments for Industrial Chemical Processes. In: Silva, V. , editor. Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes. London: IntechOpen; 2018. [CrossRef]
  • [11] Korucu, H., et al., Homogeneous graphene oxide production with the variance reduction techniques: Taguchi method with the principal component analysis. Vibrational Spectroscopy, 2019. 104: 102967. [CrossRef]
  • [12] Şimşek, B., Y.T. İç, and E.H. Şimşek, A TOPSIS-based Taguchi optimization to determine optimal mixture proportions of the high strength self-compacting concrete. Chemometrics and Intelligent Laboratory Systems, 2013. 125: 18-32. [CrossRef]
  • [13] Taguchi, G., S. Chowdhury, and Y. Wu, Taguchi's quality engineering handbook. 2005: Wiley.
  • [14] Taguchi, G. and Y. Wu, Taguchi methods: case studies from the US and Europe. Vol. 6. 1989: Amer Supplier Inst.
  • [15] Ross, P.J. and P.J. Ross, Taguchi techniques for quality engineering: loss function, orthogonal experiments, parameter and tolerance design. 1988: McGraw-Hill New York.
  • [16] Simsek, B., et al., Improvement of the graphene oxide dispersion properties with the use of TOPSIS based Taguchi application. Periodica Polytechnica Chemical Engineering 62(3), 323-335, 2018. [CrossRef]
  • [17] Şimşek, B., et al., PID control performance improvement for a liquid Level system using parameter design. International Journal of Applied Mathematics Electronics and Computers, 2016(Special Issue-1): 98-103. [CrossRef]
  • [18] Ching, L.H. and P. Yoon, Multiple Attribute Decision Making In: Lecture Notes in Economics and Mathematical Systems. 1981, Springer-Verlag, Berlin
  • [19] Sen Gupta, A., Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2016. 8(2): 255-70. [CrossRef]
  • [20] Augustine, R., et al., Cellular uptake and retention of nanoparticles: Insights on particle properties and interaction with cellular components. Materials Today Communications, 2020. 25: 101692. [CrossRef]
  • [21] Chen, L., et al., The toxicity of silica nanoparticles to the immune system. Nanomedicine, 2018. 13(15): 1939-1962. [CrossRef]
  • [22] Agotegaray, M., Amorphous Silica Nanoparticles: Biocompatibility and Biodistribution, in Silica-Based Nanotechnology for Bone Disease Treatment, M. Agotegaray, Editor. 2020, Springer International Publishing: Cham. 45-58.
  • [23] Asefa, T. and Z. Tao, Biocompatibility of Mesoporous Silica Nanoparticles. Chemical Research in Toxicology, 2012. 25(11): 2265-2284. [CrossRef]
  • [24] Tonbul, H., et al., Folic acid decoration of mesoporous silica nanoparticles to increase cellular uptake and cytotoxic activity of doxorubicin in human breast cancer cells. Journal of Drug Delivery Science and Technology, 2021. 63: 102535. [CrossRef]
  • [25] Ultav, G., et al., pH-sensitive chitosan-PEG-decorated hollow mesoporous silica nanoparticles could be an effective treatment for acute myeloid leukemia (AML). Journal of Nanoparticle Research, 2022. 24(2): 40. [CrossRef]
  • [26] Cauda, V., C. Argyo, and T. Bein, Impact of different PEGylation patterns on the long-term bio-stability of colloidal mesoporous silica nanoparticles. Journal of Materials Chemistry, 2010. 20(39): 8693-8699. [CrossRef]
  • [27] Mohamed Isa, E.D., et al., Progress in Mesoporous Silica Nanoparticles as Drug Delivery Agents for Cancer Treatment. Pharmaceutics, 2021. 13(2): 152. [CrossRef]
  • [28] Tram Nguyen, T.N., et al., Surface PEGylation of hollow mesoporous silica nanoparticles via aminated intermediate. Progress in Natural Science: Materials International, 2019. 29(6): 612-616. [CrossRef]
  • [29] Watermann, A. and J. Brieger, Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer. Nanomaterials, 2017. 7(7): 189. [CrossRef]
  • [30] Fang, X., et al., Self-templating synthesis of hollow mesoporous silica and their applications in catalysis and drug delivery. Nanoscale, 2013. 5(6): 2205-18. [CrossRef]
  • [31] González-Álvarez, R.J., et al., Experimental design applied to optimisation of silica nanoparticles size obtained by sonosynthesis. Journal of Sol-Gel Science and Technology, 2016. 80(2): 378-388. [CrossRef]
  • [32] Fernandes, R.S., I.M. Raimundo, and M.F. Pimentel, Revising the synthesis of Stöber silica nanoparticles: A multivariate assessment study on the effects of reaction parameters on the particle size. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019. 577: 1-7. [CrossRef]
  • [33] Fang, X., et al., A cationic surfactant assisted selective etching strategy to hollow mesoporous silica spheres. Nanoscale, 2011. 3(4): 1632-9. [CrossRef]

Yıl 2023, Cilt: 27 Sayı: 1, 12 - 22, 28.06.2025

Gözde Ultav Hayrettin Tonbul , Adem Şahin , Yılmaz Çapan

Öz

Kaynakça

  • [1] Akhter, F., Rao, A.A., Abbasi, M.N. et al. A Comprehensive Review of Synthesis, Applications and Future Prospects for Silica Nanoparticles (SNPs). Silicon, 2022. [CrossRef]
  • [2] Stöber, W., A. Fink, and E. Bohn, Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science, 1968. 26(1): 62-69. [CrossRef]
  • [3] Rahman, I.A. and V. Padavettan, Synthesis of Silica Nanoparticles by Sol-Gel: Size-Dependent Properties, Surface Modification, and Applications in Silica-Polymer Nanocomposites—A Review. Journal of Nanomaterials, 2012. [CrossRef]
  • [4] Bhakta, G., et al., Multifunctional silica nanoparticles with potentials of imaging and gene delivery. Nanomedicine: Nanotechnology, Biology and Medicine, 2011. 7(4): 472-479. [CrossRef]
  • [5] M. Ways, T.M.; Ng, K.W.; Lau, W.M.; Khutoryanskiy, V.V. Silica Nanoparticles in Transmucosal Drug Delivery. Pharmaceutics, 2020. 12(8): 751-775. [CrossRef]
  • [6] Prabha, S., et al., Effect of size on biological properties of nanoparticles employed in gene delivery. Artificial Cells, Nanomedicine, and Biotechnology, 2016. 44(1): 83-9110. [CrossRef]
  • [7] Sahin, A., et al., A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles’ characteristics and efficacy of intracellular delivery. Artificial Cells, Nanomedicine, and Biotechnology, 2017. 45(8): 1657-1664. [CrossRef]
  • [8] Kumar Khanna, V., Targeted delivery of nanomedicines. ISRN pharmacology, 2012. 2012: 571394-571394. [CrossRef]
  • [9] Phadke, M.S., Quality Engineering Using Robust Design, PTR Prentice-Hall. Inc., Englewood Cliffs, NJ, 1989
  • [10] Davis, R. , John, P. . Application of Taguchi-Based Design of Experiments for Industrial Chemical Processes. In: Silva, V. , editor. Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes. London: IntechOpen; 2018. [CrossRef]
  • [11] Korucu, H., et al., Homogeneous graphene oxide production with the variance reduction techniques: Taguchi method with the principal component analysis. Vibrational Spectroscopy, 2019. 104: 102967. [CrossRef]
  • [12] Şimşek, B., Y.T. İç, and E.H. Şimşek, A TOPSIS-based Taguchi optimization to determine optimal mixture proportions of the high strength self-compacting concrete. Chemometrics and Intelligent Laboratory Systems, 2013. 125: 18-32. [CrossRef]
  • [13] Taguchi, G., S. Chowdhury, and Y. Wu, Taguchi's quality engineering handbook. 2005: Wiley.
  • [14] Taguchi, G. and Y. Wu, Taguchi methods: case studies from the US and Europe. Vol. 6. 1989: Amer Supplier Inst.
  • [15] Ross, P.J. and P.J. Ross, Taguchi techniques for quality engineering: loss function, orthogonal experiments, parameter and tolerance design. 1988: McGraw-Hill New York.
  • [16] Simsek, B., et al., Improvement of the graphene oxide dispersion properties with the use of TOPSIS based Taguchi application. Periodica Polytechnica Chemical Engineering 62(3), 323-335, 2018. [CrossRef]
  • [17] Şimşek, B., et al., PID control performance improvement for a liquid Level system using parameter design. International Journal of Applied Mathematics Electronics and Computers, 2016(Special Issue-1): 98-103. [CrossRef]
  • [18] Ching, L.H. and P. Yoon, Multiple Attribute Decision Making In: Lecture Notes in Economics and Mathematical Systems. 1981, Springer-Verlag, Berlin
  • [19] Sen Gupta, A., Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2016. 8(2): 255-70. [CrossRef]
  • [20] Augustine, R., et al., Cellular uptake and retention of nanoparticles: Insights on particle properties and interaction with cellular components. Materials Today Communications, 2020. 25: 101692. [CrossRef]
  • [21] Chen, L., et al., The toxicity of silica nanoparticles to the immune system. Nanomedicine, 2018. 13(15): 1939-1962. [CrossRef]
  • [22] Agotegaray, M., Amorphous Silica Nanoparticles: Biocompatibility and Biodistribution, in Silica-Based Nanotechnology for Bone Disease Treatment, M. Agotegaray, Editor. 2020, Springer International Publishing: Cham. 45-58.
  • [23] Asefa, T. and Z. Tao, Biocompatibility of Mesoporous Silica Nanoparticles. Chemical Research in Toxicology, 2012. 25(11): 2265-2284. [CrossRef]
  • [24] Tonbul, H., et al., Folic acid decoration of mesoporous silica nanoparticles to increase cellular uptake and cytotoxic activity of doxorubicin in human breast cancer cells. Journal of Drug Delivery Science and Technology, 2021. 63: 102535. [CrossRef]
  • [25] Ultav, G., et al., pH-sensitive chitosan-PEG-decorated hollow mesoporous silica nanoparticles could be an effective treatment for acute myeloid leukemia (AML). Journal of Nanoparticle Research, 2022. 24(2): 40. [CrossRef]
  • [26] Cauda, V., C. Argyo, and T. Bein, Impact of different PEGylation patterns on the long-term bio-stability of colloidal mesoporous silica nanoparticles. Journal of Materials Chemistry, 2010. 20(39): 8693-8699. [CrossRef]
  • [27] Mohamed Isa, E.D., et al., Progress in Mesoporous Silica Nanoparticles as Drug Delivery Agents for Cancer Treatment. Pharmaceutics, 2021. 13(2): 152. [CrossRef]
  • [28] Tram Nguyen, T.N., et al., Surface PEGylation of hollow mesoporous silica nanoparticles via aminated intermediate. Progress in Natural Science: Materials International, 2019. 29(6): 612-616. [CrossRef]
  • [29] Watermann, A. and J. Brieger, Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer. Nanomaterials, 2017. 7(7): 189. [CrossRef]
  • [30] Fang, X., et al., Self-templating synthesis of hollow mesoporous silica and their applications in catalysis and drug delivery. Nanoscale, 2013. 5(6): 2205-18. [CrossRef]
  • [31] González-Álvarez, R.J., et al., Experimental design applied to optimisation of silica nanoparticles size obtained by sonosynthesis. Journal of Sol-Gel Science and Technology, 2016. 80(2): 378-388. [CrossRef]
  • [32] Fernandes, R.S., I.M. Raimundo, and M.F. Pimentel, Revising the synthesis of Stöber silica nanoparticles: A multivariate assessment study on the effects of reaction parameters on the particle size. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019. 577: 1-7. [CrossRef]
  • [33] Fang, X., et al., A cationic surfactant assisted selective etching strategy to hollow mesoporous silica spheres. Nanoscale, 2011. 3(4): 1632-9. [CrossRef]
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Gözde Ultav 0000-0001-5582-3766

Hayrettin Tonbul 0000-0001-5510-8973

Adem Şahin 0000-0002-3996-2931

Yılmaz Çapan 0000-0003-1234-9018

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 1

Kaynak Göster

APA Ultav, G., Tonbul, H., Şahin, A., Çapan, Y. (2025). Silica nanoparticle synthesis by experimental design for drug and gene delivery applications. Journal of Research in Pharmacy, 27(1), 12-22.
AMA Ultav G, Tonbul H, Şahin A, Çapan Y. Silica nanoparticle synthesis by experimental design for drug and gene delivery applications. J. Res. Pharm. Haziran 2025;27(1):12-22.
Chicago Ultav, Gözde, Hayrettin Tonbul, Adem Şahin, ve Yılmaz Çapan. “Silica Nanoparticle Synthesis by Experimental Design for Drug and Gene Delivery Applications”. Journal of Research in Pharmacy 27, sy. 1 (Haziran 2025): 12-22.
EndNote Ultav G, Tonbul H, Şahin A, Çapan Y (01 Haziran 2025) Silica nanoparticle synthesis by experimental design for drug and gene delivery applications. Journal of Research in Pharmacy 27 1 12–22.
IEEE G. Ultav, H. Tonbul, A. Şahin, ve Y. Çapan, “Silica nanoparticle synthesis by experimental design for drug and gene delivery applications”, J. Res. Pharm., c. 27, sy. 1, ss. 12–22, 2025.
ISNAD Ultav, Gözde vd. “Silica Nanoparticle Synthesis by Experimental Design for Drug and Gene Delivery Applications”. Journal of Research in Pharmacy 27/1 (Haziran 2025), 12-22.
JAMA Ultav G, Tonbul H, Şahin A, Çapan Y. Silica nanoparticle synthesis by experimental design for drug and gene delivery applications. J. Res. Pharm. 2025;27:12–22.
MLA Ultav, Gözde vd. “Silica Nanoparticle Synthesis by Experimental Design for Drug and Gene Delivery Applications”. Journal of Research in Pharmacy, c. 27, sy. 1, 2025, ss. 12-22.
Vancouver Ultav G, Tonbul H, Şahin A, Çapan Y. Silica nanoparticle synthesis by experimental design for drug and gene delivery applications. J. Res. Pharm. 2025;27(1):12-2.