Optimisation Studies of Mesoporous Silica Nanoparticle as a Drug Carrier for Gemcitabine: Enhancing Therapeutic Effectiveness in Pancreatic Cancer

Abstract:

Pancreatic cancer, often referred to as “the silent killer”, presents with minimal or no symptoms in its early stages, leading to late detection when surgical resection is no longer the optimal treatment option. Gemcitabine (GEM), one of the leading chemotherapeutic drug for advanced stages of cancer, is a crucial treatment for pancreatic cancer. However, the low 5-year survival rate of pancreatic cancer patients highlight the limited effectiveness of current treatments. In recent years, mesoporous silica nanoparticles (MSNP) have garnered significant attention in both scholarly and pharmaceutical fields due to their unique combination of properties including stable porous structure and high loading capacities. This research aims to investigate the potential of MSNP as a carrier for anticancer drugs, specifically GEM. MSNP was successfully synthesized in the laboratory using sol-gel method with tetraethyl orthosilicate (TEOS) as silica source and cetyltrimethylammonium bromide (CTAB) as surfactant template. Comprehensive morphological and physical characterizations of the MSNP product were performed through transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) spectroscopy, element mapping, X-ray diffractometry (XRD), and accelerated surface area porosimetry (ASAP). The results demonstrate that MSNP exhibits desirable properties for drug loading, including a stable mesoporous structure with pore size of ~ 4.94 nm, a high surface area of about 278.32 m²/g, and average particle diameter of approximately 85 nm. The effects of incubation time and initial GEM concentrations were studied to determine the optimal drug loading parameters for the MSNP vehicle. The successful loading of up to 24 µg of GEM in 1 mg of MSNP achieved in an optimized incubation time of 2 hour, validates the tremendous potential of MSNP as a potential anticancer drug carrier in pancreatic cancer treatment. These findings provide a valuable reference for future research and investigations in this promising field.

• Periodical: Key Engineering Materials (Volume 977)
• Pages: 155-162
• DOI: https://doi.org/10.4028/p-PdcI7G
• Online since: March 2024
• Authors: Shei Li Chung, Wei Meng Lim, Chee Onn Leong, Maxine Swee Li Yee*
• Keywords: Drug Loading, Gemcitabine, Mesoporous Silica Nanoparticle, Pancreatic Cancer

References

[1] J.D. Mizrahi, R. Surana, J.W. Valle, R.T. Shroff, Pancreatic cancer, The Lancet. 395 (2020) 2008–2020.

DOI: 10.1016/s0140-6736(20)30974-0

[2] T. Kamisawa, L.D. Wood, T. Itoi, K. Takaori, Pancreatic cancer, The Lancet. 388 (2016) 73–85.

DOI: 10.1016/s0140-6736(16)00141-0

[3] M. Ilic, I. Ilic, Epidemiology of pancreatic cancer, World J Gastroenterol. 22 (2016) 9694–9705.

[4] J. Kleeff, M. Korc, M. Apte, C. La Vecchia, C.D. Johnson, A. V. Biankin, R.E. Neale, M. Tempero, D.A. Tuveson, R.H. Hruban, J.P. Neoptolemos, Pancreatic cancer, Nat Rev Dis Primers. 2 (2016) 1–23.

DOI: 10.1038/nrdp.2016.22

[5] Cancer Statistics for the UK, (n.d.). https://www.cancerresearchuk.org/health-professional/cancer-statistics-for-the-uk (accessed August 2, 2023).

[6] P.S. Sushma, G.P. Nagaraju, Pancreatic Cancer Resistance to Gemcitabine, Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy. (2019) 45–56.

DOI: 10.1016/b978-0-12-817661-0.00004-4

[7] T.L. Gastroenterology, Editorial Pancreatic cancer : a state of emergency ?, Lancet Gastroenterol Hepatol. 6 (2021) 81.

[8] L. Zhou, H. Wang, Y. Li, Stimuli-responsive nanomedicines for overcoming cancer multidrug resistance, Theranostics. 8 (2018) 1059–1074.

DOI: 10.7150/thno.22679

[9] M. Filipits, Mechanisms of cancer: Multidrug resistance, Drug Discov Today Dis Mech. 1 (2004) 229–234.

DOI: 10.1016/j.ddmec.2004.10.001

[10] M. Saraswathy, S. Gong, Different strategies to overcome multidrug resistance in cancer, Biotechnol Adv. 31 (2013) 1397–1407.

DOI: 10.1016/j.biotechadv.2013.06.004

[11] K. Samanta, S. Setua, S. Kumari, M. Jaggi, M.M. Yallapu, S.C. Chauhan, Gemcitabine combination nano therapies for pancreatic cancer, Pharmaceutics. 11 (2019) 1–25.

DOI: 10.3390/pharmaceutics11110574

[12] S.L. Chung, M.S.L. Yee, L.W. Hii, W.M. Lim, M.Y. Ho, P.S. Khiew, C.O. Leong, Advances in nanomaterials used in co-delivery of sirna and small molecule drugs for cancer treatment, Nanomaterials. 11 (2021) 1–20.

DOI: 10.3390/nano11102467

[13] S. Paroha, J. Verma, R.D. Dubey, R.P. Dewangan, N. Molugulu, R.A. Bapat, P.K. Sahoo, P. Kesharwani, Recent advances and prospects in gemcitabine drug delivery systems, Int J Pharm. 592 (2021) 120043.

DOI: 10.1016/j.ijpharm.2020.120043

[14] J. Lu, M. Liong, Z. Li, J.I. Zink, F. Tamanoi, Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals, Small. 6 (2010) 1794–1805.

DOI: 10.1002/smll.201000538

[15] R. Yuvakkumar, V. Elango, V. Rajendran, N. Kannan, High-purity nano silica powder from rice husk using a simple chemical method, J Exp Nanosci. 9 (2014) 272–281.

DOI: 10.1080/17458080.2012.656709

[16] F. Ghorbani, A.M. Sanati, M. Maleki, Production of Silica Nanoparticles from Rice Husk as Agricultural Waste by Environmental Friendly Technique, Environmental Studies of Persian Gulf. 2 (2015) 56–65.

[17] S. Song, H.B. Cho, H.T. Kim, Surfactant-free synthesis of high surface area silica nanoparticles derived from rice husks by employing the Taguchi approach, Journal of Industrial and Engineering Chemistry. 61 (2018) 281–287.

DOI: 10.1016/j.jiec.2017.12.025

[18] Y. He, S. Liang, M. Long, H. Xu, Mesoporous silica nanoparticles as potential carriers for enhanced drug solubility of paclitaxel, Materials Science and Engineering C. 78 (2017) 12–17.

DOI: 10.1016/j.msec.2017.04.049

[19] T. Li, S. Shi, S. Goel, X. Shen, X. Xie, Z. Chen, H. Zhang, S. Li, X. Qin, H. Yang, C. Wu, Y. Liu, Recent advancements in mesoporous silica nanoparticles towards therapeutic applications for cancer, Acta Biomater. 89 (2019) 1–13.

DOI: 10.1016/j.actbio.2019.02.031

[20] H. Meng, M. Liong, T. Xia, Z. Li, Z. Ji, J.I. Zink, A.E. Nel, Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and p-glycoprotein siRNA to overcome drug resistance in a cancer cell line, ACS Nano. 4 (2010) 4539–4550.

DOI: 10.1021/nn100690m

[21] T. Xia, M. Kovochich, M. Liong, H. Meng, S. Kabehie, S. George, J.I. Zink, A.E. Nel, Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs, ACS Nano. 3 (2009) 3273–3286.

DOI: 10.1021/nn900918w

[22] S.P. Hadipour Moghaddam, R. Mohammadpour, H. Ghandehari, In vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition, Journal of Controlled Release. 311–312 (2019) 1–15.

DOI: 10.1016/j.jconrel.2019.08.028

[23] S. Saroj, S.J. Rajput, Facile development, characterization, and evaluation of novel bicalutamide loaded pH-sensitive mesoporous silica nanoparticles for enhanced prostate cancer therapy, Drug Dev Ind Pharm. 45 (2019) 532–547.

DOI: 10.1080/03639045.2018.1562463

[24] J. Lu, M. Liong, J.I. Zink, F. Tamanoi, Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs, Small. 3 (2007) 1341–1346.

DOI: 10.1002/smll.200700005

[25] B. Muñoz, A. Rámila, J. Pérez-Pariente, I. Díaz, M. Vallet-Regí, MCM-41 organic modification as drug delivery rate regulator, Chemistry of Materials. 15 (2003) 500–503.

DOI: 10.1021/cm021217q

[26] S.Y. Chen, P.F. Chou, W.K. Chan, H.M. Lin, Preparation and characterization of mesoporous bioactive glass from agricultural waste rice husk for targeted anticancer drug delivery, Ceram Int. 43 (2017) 2239–2245.

DOI: 10.1016/j.ceramint.2016.11.007

[27] J. Athinarayanan, V.S. Periasamy, M. Alhazmi, K.A. Alatiah, A.A. Alshatwi, Synthesis of biogenic silica nanoparticles from rice husks for biomedical applications, Ceram Int. 41 (2015) 275–281.

DOI: 10.1016/j.ceramint.2014.08.069

[28] K. Saini, R. Bandyopadhyaya, Transferrin-Conjugated Polymer-Coated Mesoporous Silica Nanoparticles Loaded with Gemcitabine for Killing Pancreatic Cancer Cells, ACS Appl Nano Mater. 3 (2020) 229–240.

DOI: 10.1021/acsanm.9b01921

[29] Y. Cao, C. Wu, Y. Liu, L. Hu, W. Shang, Z. Gao, N. Xia, Folate functionalized pH-sensitive photothermal therapy traceable hollow mesoporous silica nanoparticles as a targeted drug carrier to improve the antitumor effect of doxorubicin in the hepatoma cell line SMMC-7721, Drug Deliv. 27 (2020) 258–268.

DOI: 10.1080/10717544.2020.1718801

[30] I.L. Hsiao, S. Fritsch-Decker, A. Leidner, M. Al-Rawi, V. Hug, S. Diabaté, S.L. Grage, M. Meffert, T. Stoeger, D. Gerthsen, A.S. Ulrich, C.M. Niemeyer, C. Weiss, Biocompatibility of Amine-Functionalized Silica Nanoparticles: The Role of Surface Coverage, Small. 15 (2019) 1–11.

DOI: 10.1002/smll.201805400