AAPS PharmSciTech

, Volume 19, Issue 3, pp 1344–1357 | Cite as

Facile Synthesis of Chitosan Capped Mesoporous Silica Nanoparticles: A pH Responsive Smart Delivery Platform for Raloxifene Hydrochloride

Research Article
  • 160 Downloads

Abstract

An encapsulation of model drug raloxifene hydrochloride (RAL) inside the chitosan decorated pH responsive mesoporous system has a greater potential for accumulating in the tumor cells. The present study involves synthesis of surface modified mesoporous silica nanoparticles (MSN) with the aim of achieving pH sensitive drug delivery system. A silanol skeleton of MSN has been productively modified to amine intermediate which served as a firm platform to adapt chitosan grafted assembly and systematically evaluated. RAL incorporation inside the featured mesopores was performed employing novel immersion solvent evaporation methodology and evaluated further. The pH responsive behavior of formulated nano framework was studied at three different pH of a phosphate buffer saline individually. The in vitro cell viability assay on MCF-7 breast carcinoma cells was performed in time and concentration dependent manner. Finally, the hemolysis assay of designed nanoparticle was accomplished to envisage the hemocompatibility. The outcome of characterization details unveiled a perfect 2D hexagonal spherical structure gifted with higher surface area and optimum pore size for designed nanoparticles. The higher percentage grafting of amine and chitosan residue, i.e., 4.01 and 28.51% respectively along with 31.89 and 33.57% RAL loading efficiency made MSNs more attractive and applicable. Eventually, in vitro release study exhibited higher RAL release in acidic media for extended time periods confirming successful formation of pH responsive nanoparticle having controlled release property. Conclusively potential of designed nanosystem to serve efficient anti-cancer remedy was confirmed by superior behaviour of chitosan grafted MSN towards MCF-7 cells with supreme hemocompatibility.

KEY WORDS

raloxifene hydrochloride anomalous release chitosan MCF-7 hemolysis assay 

Notes

Acknowledgements

The authors thank Dr. Amirali Popat, School of Pharmacy, The University of Queensland, Australia and Zydus research centre, Gujarat, India for providing RAL gift sample.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2017_949_MOESM1_ESM.jpg (78 kb)
Supplementary figure 1 FT-IR spectra of (A) RAL; (B) RAL@CTAB; (C) MSN-41 (D) MSN-NH2–41 (E) MSN-CHITO-41 (F) RAL-41 (G) RAL-NH2–41 (H) RAL-CHITO-41 (JPEG 77 kb)
12249_2017_949_MOESM2_ESM.jpg (28 kb)
Supplementary figure 2 DSC thermogram of (A) RAL; (B) RAL-41; (C) RAL-NH2–41 (D) RAL-CHITO-41 (JPEG 28 kb)
12249_2017_949_MOESM3_ESM.jpg (86 kb)
Supplementary figure 3 Hydrodynamic pore size distribution pattern for (A) MSN-41; (B) MSN-NH2–41 (C) MSN-CHITO-41 (JPEG 86 kb)
12249_2017_949_MOESM4_ESM.jpg (45 kb)
Supplementary figure 4 Supplementary fig. 4: (A) DSC and (B) WAXS data for RAL after solvent evaporation (JPEG 44 kb)
12249_2017_949_MOESM5_ESM.jpg (37 kb)
Supplementary figure 5 TGA thermogram of (A) RAL; (B) RAL-41; (C) RAL-NH2–41 (D) RAL-CHITO-41 (JPEG 36 kb)
12249_2017_949_MOESM6_ESM.jpg (24 kb)
Supplementary figure 6 TGA thermogram of (A) MSN-41; (B) MSN-NH2–41 (C) MSN-CHITO-41 (JPEG 23 kb)

References

  1. 1.
    Daryasari MP, Akhgar MR, Mamashli F, Bigdeli B, Khoobi M. Chitosan-folate coated mesoporous silica nanoparticles as a smart and pH-sensitive system for curcumin delivery. RSC Adv. 2016;6(107):105578–88.  https://doi.org/10.1039/C6RA23182A.CrossRefGoogle Scholar
  2. 2.
    de Oliveira Freitas LB, Bravo IJG, de Almeida Macedo WA, de Sousa EMB. Mesoporous silica materials functionalized with folic acid: preparation, characterization and release profile study with methotrexate. J Sol-Gel Sci Technol. 2016;77(1):186–204.  https://doi.org/10.1007/s10971-015-3844-8.CrossRefGoogle Scholar
  3. 3.
    Maleki A, Hamidi M. Dissolution enhancement of a model poorly water-soluble drug, atorvastatin, with ordered mesoporous silica: comparison of MSF with SBA-15 as drug carriers. Expert Opin Drug Deliv. 2016;13(2):171–81.  https://doi.org/10.1517/17425247.2015.1111335.CrossRefPubMedGoogle Scholar
  4. 4.
    Anirudhan T, Binusreejayan, Jayan PP. Development of functionalized chitosan-coated carboxylated mesoporous silica: a dual drug carrier. Des Monomers Polym. 2016;19(5):381–93.CrossRefGoogle Scholar
  5. 5.
    Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24(12):1504–34.  https://doi.org/10.1002/adma.201104763.CrossRefPubMedGoogle Scholar
  6. 6.
    Vadia N, Rajput S. Study on formulation variables of methotrexate loaded mesoporous MCM-41 nanoparticles for dissolution enhancement. Eur J Pharm Sci. 2012;45(1):8–18.  https://doi.org/10.1016/j.ejps.2011.10.016.CrossRefPubMedGoogle Scholar
  7. 7.
    Ganesh M, Ubaidulla U, Hemalatha P, Peng MM, Jang HT. Development of duloxetine hydrochloride loaded mesoporous silica nanoparticles: characterizations and in vitro evaluation. AAPS PharmSciTech. 2015;16(4):944–51.  https://doi.org/10.1208/s12249-014-0273-x.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bharti C, Nagaich U, Pal AK, Gulati N. Mesoporous silica nanoparticles in target drug delivery system: a review. Int J Pharm Investig. 2015;5(3):124–33.  https://doi.org/10.4103/2230-973X.160844.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Roggers R, Kanvinde S, Boonsith S, Oupický D. The practicality of mesoporous silica nanoparticles as drug delivery devices and progress toward this goal. AAPS PharmSciTech. 2014;15(5):1163–71.  https://doi.org/10.1208/s12249-014-0142-7.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gulfam M, Chung BG. Development of pH-responsive chitosan-coated mesoporous silica nanoparticles. Macromol Res. 2014;22(4):412–7.  https://doi.org/10.1007/s13233-014-2063-4.CrossRefGoogle Scholar
  11. 11.
    Wu X, Wang Z, Zhu D, Zong S, Yang L, Zhong Y, et al. pH and thermo dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles encapsulated in a copolymer–lipid bilayer. ACS Appl Mater Interfaces. 2013;5(21):10895–903.  https://doi.org/10.1021/am403092m.CrossRefPubMedGoogle Scholar
  12. 12.
    Lim E-K, Sajomsang W, Choi Y, Jang E, Lee H, Kang B, et al. Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy. Nanoscale Res Lett. 2013;8(1):467.  https://doi.org/10.1186/1556-276X-8-467.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
  14. 14.
    Ahmadi Nasab N, Hassani Kumleh H, Beygzadeh M, Teimourian S, Kazemzad M. Delivery of curcumin by a pH-responsive chitosan mesoporous silica nanoparticles for cancer treatment. Artif Cells Nanomed Biotechnol. 2017:1–7.  https://doi.org/10.1080/21691401.2017.1290648.
  15. 15.
    Lv G, Qiu L, Liu G, Wang W, Li K, Zhao X, et al. pH sensitive chitosan-mesoporous silica nanoparticles for targeted delivery of a ruthenium complex with enhanced anticancer effects. Dalton Trans. 2016;45(45):18147–55.  https://doi.org/10.1039/C6DT03783F.CrossRefPubMedGoogle Scholar
  16. 16.
    Peng H, Dong R, Wang S, Zhang Z, Luo M, Bai C, et al. A pH-responsive nano-carrier with mesoporous silica nanoparticles cores and poly (acrylic acid) shell-layers: fabrication, characterization and properties for controlled release of salidroside. Int J Pharm. 2013;446(1):153–9.  https://doi.org/10.1016/j.ijpharm.2013.01.071.CrossRefPubMedGoogle Scholar
  17. 17.
    Yuan L, Tang Q, Yang D, Zhang JZ, Zhang F, Hu J. Preparation of pH-responsive mesoporous silica nanoparticles and their application in controlled drug delivery. J Phys Chem C. 2011;115(20):9926–32.  https://doi.org/10.1021/jp201053d.CrossRefGoogle Scholar
  18. 18.
    Tang H, Guo J, Sun Y, Chang B, Ren Q, Yang W. Facile synthesis of pH sensitive polymer-coated mesoporous silica nanoparticles and their application in drug delivery. Int J Pharm. 2011;421(2):388–96.  https://doi.org/10.1016/j.ijpharm.2011.10.013.CrossRefPubMedGoogle Scholar
  19. 19.
    Li G, Liu G, Kang E, Neoh K, Yang X. pH-responsive hollow polymeric microspheres and concentric hollow silica microspheres from silica− polymer core− shell microspheres. Langmuir. 2008;24(16):9050–5.  https://doi.org/10.1021/la8010579.CrossRefPubMedGoogle Scholar
  20. 20.
    Gulzar A, Gai S, Yang P, Li C, Ansari MB, Lin J. Stimuli responsive drug delivery application of polymer and silica in biomedicine. J Mater Chem B. 2015;3(44):8599–622.  https://doi.org/10.1039/C5TB00757G.CrossRefGoogle Scholar
  21. 21.
    Jordan V. Beyond raloxifene for the prevention of osteoporosis and breast cancer. Br J Pharmacol. 2007;150(1):3–4.  https://doi.org/10.1038/sj.bjp.0706962.CrossRefPubMedGoogle Scholar
  22. 22.
    Jha RK, Tiwari S, Mishra B. Bioadhesive microspheres for bioavailability enhancement of raloxifene hydrochloride: formulation and pharmacokinetic evaluation. AAPS PharmSciTech. 2011;12(2):650–7.  https://doi.org/10.1208/s12249-011-9619-9.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Rampino A, Borgogna M, Blasi P, Bellich B, Cesàro A. Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm. 2013;455(1):219–28.  https://doi.org/10.1016/j.ijpharm.2013.07.034.CrossRefPubMedGoogle Scholar
  24. 24.
    Woraphatphadung T, Sajomsang W, Gonil P, Treetong A, Akkaramongkolporn P, Ngawhirunpat T, et al. pH-responsive polymeric micelles based on amphiphilic chitosan derivatives: effect of hydrophobic cores on oral meloxicam delivery. Int J Pharm. 2016;497(1):150–60.  https://doi.org/10.1016/j.ijpharm.2015.12.009.CrossRefPubMedGoogle Scholar
  25. 25.
    Shah PV, Rajput SJA. Comparative in vitro release study of raloxifene encapsulated ordered MCM-41 and MCM-48 nanoparticles: a dissolution kinetics study in simulated and biorelevant media. J Drug Delivery Sci Technol. 2017;41:31–44.  https://doi.org/10.1016/j.jddst.2017.06.015.CrossRefGoogle Scholar
  26. 26.
    Wouters BH, Chen T, Dewilde M, Grobet PJ. Reactivity of the surface hydroxyl groups of MCM-41 towards silylation with trimethylchlorosilane. Microporous Mesoporous Mater. 2001;44:453–7.CrossRefGoogle Scholar
  27. 27.
    Ebrahimi-Gatkash M, Younesi H, Shahbazi A, Heidari A. Amino-functionalized mesoporous MCM-41 silica as an efficient adsorbent for water treatment: batch and fixed-bed column adsorption of the nitrate anion. Appl Water Sci 2015:1–15.Google Scholar
  28. 28.
    Yoncheva K, Popova M, Szegedi A, Mihály J, Tzankov B, Lambov N, et al. Functionalized mesoporous silica nanoparticles for oral delivery of budesonide. J Solid State Chem. 2014;211:154–61.  https://doi.org/10.1016/j.jssc.2013.12.020.CrossRefGoogle Scholar
  29. 29.
    Rosen JE, Surface GFX. Functionalization of silica nanoparticles with cysteine: a low-fouling zwitterionic surface. Langmuir. 2011;27(17):10507–13.  https://doi.org/10.1021/la201940r.CrossRefPubMedGoogle Scholar
  30. 30.
    Ding Y, Shen SZ, Sun H, Sun K, Liu F, Qi Y, et al. Design and construction of polymerized-chitosan coated Fe 3 O 4 magnetic nanoparticles and its application for hydrophobic drug delivery. Mater Sci Eng C. 2015;48:487–98.  https://doi.org/10.1016/j.msec.2014.12.036.CrossRefGoogle Scholar
  31. 31.
    Lu H-T. Synthesis and characterization of amino-functionalized silica nanoparticles. Colloid J. 2013;75(3):311–8.CrossRefGoogle Scholar
  32. 32.
    de Oliveira LFA, Bouchmella K, KDA G, Bettini J, Kobarg J, Cardoso MB. Functionalized silica nanoparticles as an alternative platform for targeted drug-delivery of water insoluble drugs. Langmuir. 2016;32(13):3217–25.  https://doi.org/10.1021/acs.langmuir.6b00214.CrossRefPubMedGoogle Scholar
  33. 33.
    Zhao Y, Sun X, Zhang G, Trewyn BG, Slowing II, Lin VS-Y. Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. ACS Nano. 2011;5(2):1366–75.  https://doi.org/10.1021/nn103077k.CrossRefPubMedGoogle Scholar
  34. 34.
    Akrami M, Khoobi M, Khalilvand-Sedagheh M, Haririan I, Bahador A, Faramarzi MA, et al. Evaluation of multilayer coated magnetic nanoparticles as biocompatible curcumin delivery platforms for breast cancer treatment. RSC Adv. 2015;5(107):88096–107.  https://doi.org/10.1039/C5RA13838H.
  35. 35.
    Li J, Zheng L, Cai H, Sun W, Shen M, Zhang G, et al. Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging. Biomaterials. 2013;34(33):8382–92.  https://doi.org/10.1016/j.biomaterials.2013.07.070.CrossRefPubMedGoogle Scholar
  36. 36.
    Charnay C, Bégu S, Tourné-Péteilh C, Nicole L, Lerner D, Devoisselle J-M. Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property. Eur J Pharm Biopharm. 2004;57(3):533–40.  https://doi.org/10.1016/j.ejpb.2003.12.007.CrossRefPubMedGoogle Scholar
  37. 37.
    Patil A, Chirmade U, Trivedi V, Lamprou D, Urquart A, Douroumis D. Encapsulation of water insoluble drugs in mesoporous silica nanoparticles using supercritical carbon dioxide. Journal of Nanomedicine and Nanotechnology 2011;2(3).Google Scholar
  38. 38.
    Carriazo D, Del Arco M, Fernández A, Martín C, Rives V. Inclusion and release of fenbufen in mesoporous silica. J Pharm Sci. 2010;99(8):3372–80.  https://doi.org/10.1002/jps.22096.CrossRefPubMedGoogle Scholar
  39. 39.
    Mahdavinia G, Pourjavadi A, Hosseinzadeh H, Zohuriaan M. Modified chitosan 4. Superabsorbent hydrogels from poly (acrylic acid-co-acrylamide) grafted chitosan with salt-and pH-responsiveness properties. Eur Polym J. 2004;40(7):1399–407.  https://doi.org/10.1016/j.eurpolymj.2004.01.039.CrossRefGoogle Scholar
  40. 40.
    Tan D, Yuan P, Annabi-Bergaya F, Liu D, Wang L, Liu H, et al. Loading and in vitro release of ibuprofen in tubular halloysite. Appl Clay Sci. 2014;96:50–5.  https://doi.org/10.1016/j.clay.2014.01.018.CrossRefGoogle Scholar
  41. 41.
    Seema Saroj, Sadhana J. Rajput, (2018) Etoposide encapsulated functionalized mesoporous silica nanoparticles: Synthesis, characterization and effect of functionalization on dissolution kinetics in simulated and biorelevant media. J Drug Delivery Sci Technol 44:27–40.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Faculty of Pharmacy, Centre of Relevance and Excellence in New Drug Delivery System, Government of IndiaThe Maharaja Sayajirao University of BarodaVadodaraIndia

Personalised recommendations