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Dual-responsive mesoporous poly-N-isopropylacrylamide-hydroxyapatite composite microspheres for controlled anticancer drug delivery

  • Original Paper: Sol-gel and hybrid materials for biological and health (medical) applications
  • Published:
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Abstract

The advantages of mesoporous hydroxyapatite and the thermo-responsive property of poly-N-isopropylacrylamide make them attractive in drug delivery system, respectively. In this work, mesoporous poly-N-isopropylacrylamide-hydroxyapatite composite microspheres (PNIPAM-m-HAP) were synthesized, characterized and applied as a drug carrier. Doxorubicin was selected as a typical anticancer drug to study the in-vitro release characteristics of drug from PNIPAM-m-HAP in PBS. The release mechanism and release kinetics was also studied. Furthermore, the biocompatibility of the PNIPAM-m-HAP material was evaluated by MTT method. The experimental results depicted that the synthesized PNIPAM-m-HAP material was biocompatible, pH and thermo-responsive, which showed controlled release of doxorubicin.

Mesoporous hydroxyapatite and poly-N-isopropylacrylamide composite microspheres were synthesized, characterized and applied as a drug carrier for anticancer drug of doxorubicin, which showed controlled release of doxorubicin and dual response of pH and temperature.

Highlights

  • PNIPAM-m-HAP microspheres were synthesized, characterized and used as anticancer drug carrier.

  • PNIPAM-m-HAP was pH and thermo-responsive, which showed sustainable release of doxorubicin.

  • The release mechanism was studied and the biocompatibility of PNIPAM-m-HAP was evaluated.

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References

  1. Manzano M, Regí MV (2010) New developments in ordered mesoporous materials for drug delivery. J Mater Chem 20:5593–5604

    Article  CAS  Google Scholar 

  2. Regí MV, Balas F, Arcos D (2007) Mesoporous materials for drug delivery. Angew Chem Int Ed 46(40):7548–7558

    Article  Google Scholar 

  3. Pritam S, Kamalika S (2018) Contemporary mesoporous materials for drug delivery applications: a review. J Porous Mater 25(4):965–987

    Article  Google Scholar 

  4. Kwon S, Singh RK, Perez RA, Neel EAA, Kim HW, Chrzanowski W (2013) Silica-based mesoporous nanoparticles for controlled drug delivery. J Tissue Eng 4:1–18

    Article  Google Scholar 

  5. Mathew A, Parambadath S, Park SS, Ha CS (2014) Hydrophobically modified spherical MCM-41 as nanovalve system for controlled drug delivery. Micropor Mesopor Mat 200:124–131

    Article  CAS  Google Scholar 

  6. Nguyen TPB, Lee J, Shim WG, Moon H (2008) Synthesis of functionalized Sba-15 with ordered large pore size and its adsorption properties of Bsa. Micropor Mesopor Mat 110(2-3):560–569

    Article  CAS  Google Scholar 

  7. Yang M, Zhang NN, Zhang T, Yin X, Shen J (2020) Fabrication of doxorubicin-gated mesoporous polydopamine nanoplatforms for multimode imaging-guided synergistic chemophotothermal therapy of tumors. Drug Deliv 27(1):367–377

    Article  CAS  Google Scholar 

  8. Wu X, Zheng YW, Yang D, Chen TJ, Feng B, Weng J, Wang JX, Zhang K, Zhang XD (2019) A strategy using mesoporous polymer nanospheres as nanocarriers of Bcl-2 siRNA towards breast cancer therapy. J Mater Chem B 7:477–487

    Article  CAS  Google Scholar 

  9. Saha D, Warren KE, Naskar AK (2014) Soft-templated mesoporous carbons as potential materials for oral drug delivery. Carbon 71:47–57

    Article  CAS  Google Scholar 

  10. Tian Y, Hong J, Pan YF, Wang SH, Wang XF (2014) Adsorption of bovine serum albumin onto magnetic dual-mesoporous carbon microspheres. J Nanopart Res 16:2730–2736

    Article  Google Scholar 

  11. Asghar K, Qasim M, Dharmapuri G, Das D (2017) Investigation on a smart nanocarrier with a mesoporous magnetic core and thermo-responsive shell for co-delivery of doxorubicin and curcumin: a new approach towards combination therapy of cancer. RSC Adv 7:28802–28818

    Article  CAS  Google Scholar 

  12. Shi ZM, Zeng YZ, Chen X, Zhou F, Zheng LY, Wang GS, Gao J, Ma YY, Zheng LH, Fu B, Yu RT (2020) Mesoporous superparamagnetic cobalt ferrite nanoclusters: Synthesis, characterization and application in drug delivery. J Magn Magn Mater 498:166222

    Article  CAS  Google Scholar 

  13. Yang H, Hao LJ, Zhao NR, Du C, Wang YJ (2013) Hierarchical porous hydroxyapatite microsphere as drug delivery carrier. Cryst Eng Comm 15(29):5760–5763

    Article  CAS  Google Scholar 

  14. Safi S, Karimzadeh F, Labbaf S (2018) Mesoporous and hollow hydroxyapatite nanostructured particles as a drug delivery vehicle for the local release of ibuprofen. Mater Sci Eng C Mater Biol Appl 92:712–719

    Article  CAS  Google Scholar 

  15. Yang PP, Quan ZW, Li CX, Kang XJ, Lian HZ, Lin J (2008) Bioactive, luminescent and mesoporous europium-doped hydroxyapatite as a drug carrier. Biomaterials 29(32):4341–4347

    Article  CAS  Google Scholar 

  16. Qiao W, Lan XM, Tsoi JKH, Chen ZF, Su RYX, Yeung KWK, Matinlinna JP (2017) Biomimetic hollow mesoporous hydroxyapatite microsphere with controlled morphology, entrapment efficiency and degradability for cancer therapy. RSC Adv 7:44788–44798

    Article  CAS  Google Scholar 

  17. Zhao CX, Yu L, Middelberg APJ (2013) Magnetic mesoporous silica nanoparticles end-capped with hydroxyapatite for pH-responsive drug release. J Mater Chem B 1:4828–4833

    Article  CAS  Google Scholar 

  18. Dubnika A, Loca D, Rudovica V, Parekh MB, Cimdina LB (2017) Functionalized silver doped hydroxyapatite scaffolds for controlled simultaneous silver ion and drug delivery. Ceram Int 43(4):3698–3705

    Article  CAS  Google Scholar 

  19. Wan YZ, Cui T, Xiong GY, Li W, Tu JP, Zhu Y, Luo HL (2017) Magnetic lamellar nanohydroxyapatite as a novel nanocarrier for controlled delivery of 5-fluorouracil. Ceram Int 43(6):4957–4964

    Article  CAS  Google Scholar 

  20. Kumar GS, Govindan R, Girija EK (2014) In situ synthesis, characterization and in vitro studies of ciprofloxacin loaded hydroxyapatite nanoparticles for the treatment of osteomyelitis. J Mater Chem B 2(31):5052–5060

    Article  CAS  Google Scholar 

  21. Kang Y, Sun W, Fan JL, Wei ZM, Wang SZ, Li ML, Zhang Z, Xie YH, Du JJ, Pen XJ (2018) Ratiometric real-time monitoring of hydroxyapatite–doxorubicin nanotheranostic agents for on-demand tumor targeted chemotherapy. Mater Chem Front 2:1791–1798

    Article  CAS  Google Scholar 

  22. Kundu B, Ghosh D, Sinha MK, Sen PS, KrishnaBalla V, Das N, Basu D (2013) Doxorubicin-intercalated nano-hydroxyapatite drug-delivery system for liver cancer: An animal model. Ceram Int 39(8):9557–9566

    Article  CAS  Google Scholar 

  23. Wang S, Guo ZG (2015) Rhombohedral hydroxyapatite with mesoporous architecture for pH-responsive drug delivery. Chem Lett 44(3):279–281

    Article  Google Scholar 

  24. Samandari SS, Nezafati N, Samandari SS (2016) The effective role of hydroxyapatite based composites in anticancer drug delivery systems. Crit Rev Ther Drug Carr Syst 33(1):41–75

    Article  Google Scholar 

  25. Verma G, Barick KC, Shetake NG, Pandey BN, Hassan PA (2016) Citrate-functionalized hydroxyapatite nanoparticles for pH-responsive drug delivery. RSC Adv 6:77968–77976

    Article  CAS  Google Scholar 

  26. Foroughi F, Hassanzadeh-Tabrizi SA, Bigham A (2016) In situ microemulsion synthesis of hydroxyapatite-MgFe2O4 nanocomposite as a magnetic drug delivery system. Mat Sci Eng C 68:774–779

    Article  CAS  Google Scholar 

  27. Shin Y, Liu J, Chang JH, Exarhosa GJ (2002) Sustained drug release on temperature-responsive poly(N-isopropylacrylamide)-integrated hydroxyapatite. Chem Commun 16:1718–1719

    Article  Google Scholar 

  28. Feng DS, Shi J, Wang XJ, Li Z (2013) Hollow hybrid hydroxyapatite microparticles with sustained and pH-responsive drug delivery properties. RSC Adv 3(47):24975–24982

    Article  CAS  Google Scholar 

  29. Govindan B, Latha BS, Nagamony P, Ahmed F, Saifi MA, Harrath AH, Alwasel S, Mansour L, Alsharaeh EH (2017) Designed synthesis of nanostructured magnetic hydroxyapatite based drug nanocarrier for anti-cancer drug delivery toward the treatment of human epidermoid carcinoma. Nanomaterials 7(6):138–16

    Article  Google Scholar 

  30. Tan LC, Liu J, Zhou WH, Wei JC, Peng ZP (2014) A novel thermal and pH responsive drug delivery system based on ZnO@PNIPAM hybrid nanoparticles. Mater Sci Eng C 45:524–529

    Article  CAS  Google Scholar 

  31. Cao MW, Wang Y, Hu XZ, Gong HN, Li RH, Cox H, Zhang J, Waigh TA, Xu H, Lu JR (2019) Reversible thermoresponsive peptide–PNIPAM hydrogels for controlled drug delivery. Biomacromolecules 20(9):3601–3610

    Article  CAS  Google Scholar 

  32. Yadavalli T, Ramasamy S, Chandrasekaran G, Michael I, Therese HA, Chennakesavulu R (2015) Dual responsive PNIPAM–chitosan targeted magnetic nanopolymers for targeted drug delivery. J Magn Magn Mater 380:315–320

    Article  CAS  Google Scholar 

  33. Ashraf S, Park HK, Park H, Lee SH (2016) Snapshot of phase transition in thermoresponsive hydrogel PNIPAM: Role in drug delivery and tissue engineering. Macromol Res 24:297–304

    Article  CAS  Google Scholar 

  34. Li GY, Song S, Zhang T, Qi MY, Liu JS (2013) pH-sensitive polyelectrolyte complex micelles assembled from CS-g-PNIPAM and ALG-g-P(NIPAM-co-NVP) for drug delivery. Int J Biol Macromol 62:203–210

    Article  CAS  Google Scholar 

  35. Wu T, Tan L, Cheng N, Yan Q, Zhang YF, Liu CJ, Shi B (2016) PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment. Mater Sci Eng C 62:888–896

    Article  CAS  Google Scholar 

  36. Ritger PL, Peppas NA (1987) A simple equation for description of solute release I. Fickian and non-fickian release from nonswellable devices in the form of slabs, spheres, cylinders or discs. J Control Release 5(1):23–36

    Article  CAS  Google Scholar 

  37. Cao T, Tang WL, Zhao JC, Qin LL, Lan CB (2014) A novel drug delivery carrier based on α-eleostearic acid grafted hydroxyapatite composite. J Bionic Eng 11(1):125–133

    Article  Google Scholar 

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Acknowledgements

This work was supported by National Nature Science Foundation of China (B040603), which is from Shi Wang.

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Author notes

  1. These authors contributed equally: Liang Zhou, Yulin Zhang

Authors and Affiliations

  1. Pharmacy School, Hubei University of Science and Technology, Xianning, 437100, Hubei, China

    Liang Zhou, Yulin Zhang, Defu Zeng, Ting Shu & Shi Wang

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  1. Liang Zhou
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  2. Yulin Zhang
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  3. Defu Zeng
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  4. Ting Shu
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  5. Shi Wang
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Correspondence to Ting Shu or Shi Wang.

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Zhou, L., Zhang, Y., Zeng, D. et al. Dual-responsive mesoporous poly-N-isopropylacrylamide-hydroxyapatite composite microspheres for controlled anticancer drug delivery. J Sol-Gel Sci Technol 97, 600–609 (2021). https://doi.org/10.1007/s10971-020-05460-3

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  • DOI: https://doi.org/10.1007/s10971-020-05460-3

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