Facile Synthesis of Chitosan Capped Mesoporous Silica Nanoparticles: A pH Responsive Smart Delivery Platform for Raloxifene Hydrochloride
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 WORDSraloxifene hydrochloride anomalous release chitosan MCF-7 hemolysis assay
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.
- 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
- 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
- 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.
- 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
- 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
- 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
- 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.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
- 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
- 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
- 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