Gelatin-poly (ethylene glycol) methyl ether-functionalized porous Nanosilica for efficient doxorubicin delivery

  • Uyen Vy VoEmail author
  • Cuu Khoa Nguyen
  • Van Cuong Nguyen
  • Tuong Vi Tran
  • Bao Yen To Thi
  • Dai Hai NguyenEmail author


Porous nanosilica (PNS) has been receiving wider attention in the fabrication of nanocarriers for drug delivery. However, unmodified PNS nanoparticles have shown an initial rapid release of encapsulated drugs, which may limit their potential applications in the clinical setting. In this report, in order to improve the efficiency of drug delivery, PNS nanoparticles were first synthesized and then surface conjugated with gelatin-poly (ethylene glycol) methyl ether (GEL-mPEG) to form PNS-GEL-mPEG nanocarriers for doxorubicin (DOX) delivery. The co-polymer structure and morphology of the obtained nanocarriers were analyzed using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The loading capacity, encapsulation efficiency and DOX release behavior of DOX@PNS-GEL-mPEG nanocarriers were also evaluated. Results showed that the conjugated PNS nanocarriers were spherical shape with an average diameter of 69.60 ± 3.27 nm, as compared to 58.93 ± 2.42 nm of PNS nanocarriers. Also, the PNS-GEL-mPEG nanoparticles showed their ability to effectively encapsulate DOX. In detail, DOX was significantly encapsulated into PNS-GEL-mPEG nanocarriers to form DOX@PNS-GEL-mPEG nanocarriers with high loading efficiency of 85.88 ± 0.15%. Moreover, the synthesized DOX@PNS-GEL-mPEG nanoparticles exhibited a sustainable release of DOX up to 96 h, without a burst release, as compared with less than 2 h from unconjugated PNS nanocarriers, and exhibited a pH-dependent drug release behavior of DOX in acidic media. These results indicated that DOX@PNS-GEL-mPEG nanocarriers have high potential applications for efficient DOX loading and release in cancer therapy.


Porous nanosilica Gelatin Polyethylene glycol Drug delivery system Cancer therapy 



This research was financially supported by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 104.03-2018.46.


  1. 1.
    Xie M, Shi H, Li Z, Shen H, Ma K, Li B, Shen S, Jin Y (2013) A multifunctional mesoporous silica nanocomposite for targeted delivery, controlled release of doxorubicin and bioimaging. Colloids Surf B: Biointerfaces 110:138–147. CrossRefPubMedGoogle Scholar
  2. 2.
    Zhang Y, Chan HF, Leong KW (2013) Advanced materials and processing for drug delivery: the past and the future. Adv Drug Deliv Rev 65(1):104–120. CrossRefGoogle Scholar
  3. 3.
    Cha W, Fan R, Miao Y, Zhou Y, Qin C, Shan X, Wan X, Li J (2017) Mesoporous silica nanoparticles as carriers for intracellular delivery of nucleic acids and subsequent therapeutic applications. Molecules 22(5):782. CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Tran Tuong V, Vo Uyen V, Pham Dong Y, Tran Dai L, Nguyen Thi H, Tran Ngoc Q, Nguyen Cuu K, Thu Le V, Nguyen Dai H (2016) Supramolecular chemistry at interfaces: host-guest interactions for attaching PEG and 5-fluorouracil to the surface of porous nanosilica. Green Process Synth 5.
  5. 5.
    Adjei IM, Sharma B, Labhasetwar V (2014) Nanoparticles: cellular uptake and cytotoxicity. Nanomaterial Springer:73–91.
  6. 6.
    Satyanarayana MS, Sreenath PR, Basavaraja S, Dinesh Kumar K (2018) Unique behavior of in-situ generated nanosilica particles on physico-mechanical properties of fluoroelastomer. J Polym Res 25(11):230. CrossRefGoogle Scholar
  7. 7.
    Zhang J, Niemelä M, Westermarck J, Rosenholm JM (2014) Mesoporous silica nanoparticles with redox-responsive surface linkers for charge-reversible loading and release of short oligonucleotides. Dalton Trans 43(10):4115–4126. CrossRefPubMedGoogle Scholar
  8. 8.
    Malfanti A, Miletto I, Bottinelli E, Zonari D, Blandino G, Berlier G, Arpicco S (2016) Delivery of gemcitabine prodrugs employing mesoporous silica nanoparticles. Molecules 21(4):522. CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Thi TTN, Tran TV, Tran NQ, Nguyen CK, Nguyen DH (2017) Hierarchical self-assembly of heparin-PEG end-capped porous silica as a redox sensitive nanocarrier for doxorubicin delivery. Mater Sci Eng C 70:947–954. CrossRefGoogle Scholar
  10. 10.
    Gao Y, Chen Y, Ji X, He X, Yin Q, Zhang Z, Shi J, Li Y (2011) Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles. ACS Nano 5(12):9788–9798CrossRefGoogle Scholar
  11. 11.
    Slowing II, Vivero-Escoto JL, Wu C-W, Lin VSY (2008) Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev 60(11):1278–1288. CrossRefGoogle Scholar
  12. 12.
    Foox M, Zilberman M (2015) Drug delivery from gelatin-based systems. Expert Opin Drug Deliv 12(9):1547–1563. CrossRefGoogle Scholar
  13. 13.
    Yan H, Chen Y, Zhang J, Liu W, Chen R (2016) The role of free radicals in the photodynamic treatment of fibrotic skin diseases. In: oxygen transport to tissue XXXVIII. Springer, pp 69-74.
  14. 14.
    Tran PH, Tran TT, Vo TV, Vo CL, Lee BJ (2013) Novel multifunctional biocompatible gelatin-oleic acid conjugate: self-assembled nanoparticles for drug delivery. J Biomed Nanotechnol 9(8):1416–1431. CrossRefGoogle Scholar
  15. 15.
    Huda MK, Das PP, Baruah SD, Saikia PJ (2017) Polycaprolactone-blended gelatin microspheres and their morphological study. J Polym Res 24(5):72CrossRefGoogle Scholar
  16. 16.
    Drew VJ, Huang H-Y, Tsai Z-H, Tsai H-H, Tseng C-L (2017) Preparation of gelatin/epigallocatechin gallate self-assembly nanoparticles for transdermal drug delivery. J Polym Res 24(11):188CrossRefGoogle Scholar
  17. 17.
    Food U, Administration D (2009) The Sourcing and Processing of Gelatin to Reduce the Potential Risk Posed by Bovine Spongiform Encephalopathy (BSE) in FDA-Regulated Products for Human UseGoogle Scholar
  18. 18.
    Thi Phuong Phong N, Nguyen Dai H (2016) Gelatin as an ecofriendly natural polymer for preparing colloidal silver@gold nanobranches. Green Process Synth 5.
  19. 19.
    Suarasan S, Focsan M, Potara M, Soritau O, Florea A, Maniu D, Astilean S (2016) Doxorubicin-incorporated nanotherapeutic delivery system based on gelatin-coated gold nanoparticles: formulation, drug release, and multimodal imaging of cellular internalization. ACS Appl Mater Interfaces 8(35):22900–22913CrossRefGoogle Scholar
  20. 20.
    Wu DC, Cammarata CR, Park HJ, Rhodes BT, Ofner CM (2013) Preparation, drug release, and cell growth inhibition of a gelatin: doxorubicin conjugate. Pharm Res 30(8):2087–2096CrossRefPubMedGoogle Scholar
  21. 21.
    Zou Z, He D, He X, Wang K, Yang X, Qing Z, Zhou Q (2013) Natural gelatin capped mesoporous silica nanoparticles for intracellular acid-triggered drug delivery. Langmuir 29(41):12804–12810. CrossRefGoogle Scholar
  22. 22.
    Xu J-H, Gao F-P, Li L-L, Ma HL, Fan Y-S, Liu W, Guo S-S, Zhao X-Z, Wang H (2013) Gelatin–mesoporous silica nanoparticles as matrix metalloproteinases-degradable drug delivery systems in vivo. Microporous Mesoporous Mater 182(Supplement C):165–172. CrossRefGoogle Scholar
  23. 23.
    Xu H, Yan F, Monson EE, Kopelman R (2003) Room-temperature preparation and characterization of poly (ethylene glycol)-coated silica nanoparticles for biomedical applications. J Biomed Mater Res A 66(4):870–879. CrossRefPubMedGoogle Scholar
  24. 24.
    Grandhi TSP, Rege K (2014) Design, synthesis, and functionalization of nanomaterials for therapeutic drug delivery. Nanomaterial Springer:157–182.
  25. 25.
    Ly TU, Tran NQ, Hoang TKD, Phan KN, Truong HN, Nguyen CK (2013) Pegylated dendrimer and its effect in fluorouracil loading and release for enhancing antitumor activity. J Biomed Nanotechnol 9(2):213–220. CrossRefPubMedGoogle Scholar
  26. 26.
    Nuttelman CR, Kloxin AM, Anseth KS (2007) Temporal changes in PEG hydrogel structure influence human mesenchymal stem cell proliferation and matrix mineralization. In: fisher JP (ed) tissue engineering. Springer US, Boston, MA, pp 135-149.
  27. 27.
    Barchuk M, Čapková P, Kolská Z, Matoušek J, Poustka D, Šplíchalová L, Benada O, Munzarová M (2016) Structure and surface properties of chitosan/PEO/gelatin nanofibrous membrane. J Polym Res 23(2):20CrossRefGoogle Scholar
  28. 28.
    Chen T, Wu W, Xiao H, Chen Y, Chen M, Li J (2016) Intelligent drug delivery system based on mesoporous silica nanoparticles coated with an ultra-pH-sensitive gatekeeper and poly(ethylene glycol). ACS Macro Lett 5(1):55–58. CrossRefGoogle Scholar
  29. 29.
    Van TD, Tran NQ, Nguyen DH, Nguyen CK, Nguyen PT (2016) Injectable hydrogel composite based gelatin-PEG and biphasic calcium phosphate nanoparticles for bone regeneration. J Electron Mater 45(5):2415–2422. CrossRefGoogle Scholar
  30. 30.
    Vahidi M, Frounchi M, Dadbin S (2017) Porous gelatin/poly (ethylene glycol) scaffolds for skin cells. Soft Materials 15(1):95–102CrossRefGoogle Scholar
  31. 31.
    Hsu YG, Lin KH (2001) Preparation and properties of ABS-silica nanocomposites through sol-gel process under the catalyzation of different catalysts. J Polym Res 8(1):69–76CrossRefGoogle Scholar
  32. 32.
    Thanh VM, Nguyen TH, Tran TV, Ngoc U-TP, Ho MN, Nguyen TT, Chau YNT, Le VT, Tran NQ, Nguyen CK, Nguyen DH (2018) Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release. Mater Sci Eng C 82(Supplement C):291–298. CrossRefGoogle Scholar
  33. 33.
    Ek S, Root A, Peussa M, Niinistö L (2001) Determination of the hydroxyl group content in silica by thermogravimetry and a comparison with 1H MAS NMR results. Thermochim Acta 379(1):201–212. CrossRefGoogle Scholar
  34. 34.
    Sun J, Zhuang G, Wu S, Zhang Z (2016) Structure and performance of anionic–cationic-organo-montmorillonite in different organic solvents. RSC Adv 6(60):54747–54753. CrossRefGoogle Scholar
  35. 35.
    Bin Ahmad M, Lim JJ, Shameli K, Ibrahim NA, Tay MY (2011) Synthesis of silver nanoparticles in chitosan, gelatin and chitosan/gelatin bionanocomposites by a chemical reducing agent and their characterization. Molecules 16(9):7237–7248. CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Zhuang C, Tao F, Cui Y (2015) Anti-degradation gelatin films crosslinked by active ester based on cellulose. RSC Adv 5(64):52183–52193. CrossRefGoogle Scholar
  37. 37.
    Gaumet M, Vargas A, Gurny R, Delie F (2008) Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. Eur J Pharm Biopharm 69(1):1–9. CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Uyen Vy Vo
    • 1
    • 2
    • 3
    Email author
  • Cuu Khoa Nguyen
    • 1
    • 2
  • Van Cuong Nguyen
    • 3
  • Tuong Vi Tran
    • 1
    • 2
  • Bao Yen To Thi
    • 2
    • 4
  • Dai Hai Nguyen
    • 1
    • 2
    Email author
  1. 1.Graduate University of Science and TechnologyVietnam Academy of Science and TechnologyHanoiVietnam
  2. 2.Institute of Applied Materials ScienceVietnam Academy of Science and TechnologyHo Chi Minh CityVietnam
  3. 3.Industrial University of Ho Chi Minh CityHo Chi Minh CityVietnam
  4. 4.Mien Tay Construction UniversityVinh Long CityVietnam

Personalised recommendations