İnsan Karaciğer Kanserinde İlaç Taşıyıcı Sistem Olarak Serisin-Montmorillonit Kompozit Nanopartiküller: Geliştirilmesi, İlaç salımı, Hücresel Alım ve Sitotoksisite

Abstract

Bilimsel ve iyileştiri özelliklerinden dolayı kompozit nanopartiküller artan ilgi görmüşlerdir. Burada, doğal kaynaklardan serisinin biyolojik olarak parçalanabilirliği ve fonksiyonel yüzey çeşitliliği ile montmorillonitin biyolojik uyumluluk ve yüksek adsorpsiyon özelliklerinden yararlanılarak serisin-montmorillonit kompozit nanopartiküller (Ser-Mt NPs) sentezlenmiştir. Kompozit nanopartiküller ilk defa desolvasyon tekniği ile sentezlenmiş ve glutaraldehit ile çapraz bağlanmıştır. Doksorubisin, yükleme ve salım çalışmalarını gerçekleştirmek için model antikanser ilaç olarak seçilmiştir. Zayıflatılmış Toplam Yansıma - Fourier Dönüşümü Kızılötesi Spektroskopisi ve Taramalı Elektron Mikroskobu gibi çeşitli yöntemlerle yapılan kimyasal ve morfolojik karakterizasyon çalışmaları sonrasında Ser-Mt kompozit NP'lerin sitotoksik etkisi, HepG2 (insan karaciğer kanseri hücre hattı) hücreleri üzerinde kalitatif ve kantitatif olarak değerlendirilmiştir. Sonuçlar, yüksek ilaç yükleme kapasitesi, sürdürülebilir ilaç salım özelliği ve kanser hücreleri üzerindeki etkisinin, monodispers, küçük ortalama boyut dağılımı ve iyi çoklu dağılım indeksine sahip Ser-Mt kompozit NP'lerini, kanser terapisi için ilaç dağıtım sistemi olarak iyi bir aday olduğunu açıkça göstermiştir.

Keywords

• Serisin
• Montmorillonit
• Kompozit nanopartiküller
• Doksorubisin
• İlaç Dağıtım

Sericin-Montmorillonite Composite Nanoparticles as Drug Delivery System in Human Liver Cancer: Development, Drug Release, Cellular Uptake and Cytotoxicity

Abstract

Composite nanoparticles obtained increasing interest because of their scientific and curative importance. Herein, sericin-montmorillonite composite nanoparticles (Ser-Mt NPs) were synthesized by taking advantage of the biodegradability and functional surface diversity of sericin, and biocompatibility and high adsorption properties of montmorillonite as natural resources. The composite nanoparticle was obtained by the desolvation technique and crosslinked with glutaraldehyde for the first time. Doxorubicin was selected to be used as a model anticancer drug to perform the loading and release studies. After chemical and morphological characterization studies with various methods such as Fourier Transform Infra-Red Spectroscopy and Electron Microscopy, the cytotoxic effect of Ser-Mt composite NPs were quanlitatively and quantitatively evaluated on HepG2 (human liver cancer cell line) cells. The results obviously exhibited that high drug loading capacity, sustainable drug release property and its effect on cancer cells made Ser-Mt composite NPs as a good candidate as a drug delivery system on cancer therapy with monodisperse, small average size and good polydispersity index.

Keywords

• Sericin
• Montmorillonite
• Composite nanoparticles
• Doxorubicin
• Drug delivery

Thanks

I want to thank Prof. Dr Serdar ABACI and Yesim Tugce YAMAN for their technical support, expertise, and stimulating discussions.

References

1. [1] Murray, H.H. 2000. Traditional and new applications for kaolin, smectite, and palygorskite: a general overview. Applied Clay Science. 17, 207–221.
2. [2] Uddin, F. 2008. Clays, nanoclays, and montmorillonite minerals, Metallurgical and Materials Transactions A-Physical Metallurgy and Materials Science, 39, 2804–2814.
3. [3] Yao, B.O., Li, C., Yang, F.E.I., Sun, G. 2018. Isothermal crystallization properties and improved rheological performance of waxy crude oil using polyoctadecylacrylate - Modified montmorillonite composite as a pour point depressant, Clays and Clay Mineral, 66, 233–244.
4. [4] Velde, B. 1992. Introduction to Clay Minerals, Springer, Dordrecht.
5. [5] Brigatti, M.F., Galn, E., Theng, B.K.G. 2013. Structure and Mineralogy of Clay Minerals.
6. [6] Schoonheydt, R.A., Johnston, C.T. 2011. The surface properties of clay minerals. Layered Mineral Structures and their Application in Advanced Technologies. 335–370.
7. [7] B. Velde. 1977. Clays and Clay Minerals In Natural And Synthetic Systems, 21st ed., Elsevier Scientific Publishing Company, New York.
8. [8] Hernández, K.A.H. 2016. Polymer-Clay Nanocomposites and Composites: Structures, Characteristics, and their Applications in the Removal of Organic Compounds of Environmental Interest, Medicinal Chemistry, 6, 201–210.

9. [9] Gupta, D., Agrawal, A., Rangi, A. 2014. Extraction and characterization of silk sericin, Indian Journal of Fibre Textile Research, 39, 364–372.
10. [10] Zhang, Y.Q. 2002. Applications of natural silk protein sericin in biomaterials, Biotechnology Advances, 20, 91–100.
11. [11] Das, S.K., Dey, T., Kundu, S.C. 2014. Fabrication of sericin nanoparticles for controlled gene delivery, RSC Advances, 4, 2137–2142.
12. [12] Dong, Y., Feng, S.S., 2005. Poly (D,L-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs, Biomaterials, 26, 6068–6076.
13. [13] Akbal, O., Vural, T., Malekghasemi, S., Bozdoğan, B., Denkbaş, E.B. 2018. Saponin loaded montmorillonite-human serum albumin nanocomposites as drug delivery system in colorectal cancer therapy, Applied Clay Science. 166, 214–222.
14. [14] Hu, Y., Xie, J., Tong, Y.W., Wang, C.H. 2007. Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells, Journal of Controlled Release, 118, 7–17.
15. [15] Akbal, Ö., Erdal, E., Vural, T., Kavaz, D., Denkbaş, E.B. 2017. Comparison of protein- and polysaccharide-based nanoparticles for cancer therapy: synthesis, characterization, drug release, and interaction with a breast cancer cell line, Artificial Cells, Nanomedicine and Biotechnology, 45, 193–203.
16. [16] Sarmah, M., Banik, N., Hussain, A., Ramteke, A., Sharma, H.K., Maji, T.K. 2015. Study on crosslinked gelatin/montmorillonite nanoparticles for controlled drug delivery applications, Journal of Material Science, 50, 7303–7313.
17. [17] Huang, L., Tao, K., Liu, J., Qi, C., Xu, L., Chang, P., Gao, J., Shuai, X., Wang, G., Wang, Z., Wang, L. 2016. Design and Fabrication of Multifunctional Sericin Nanoparticles for Tumor Targeting and pH-Responsive Subcellular Delivery of Cancer Chemotherapy Drugs, ACS Applied Materials & Interfaces, 8, 6577–6585.
18. [18] Langer, K., Anhorn, M.G., Steinhauser, I., Dreis, S., Celebi, D., Schrickel, N., Faust, S., Vogel, V. 2008. Human serum albumin (HSA) nanoparticles: Reproducibility of preparation process and kinetics of enzymatic degradation, International Journal of Pharmacology, 347, 109–117.
19. [19] Harun, F.W., Almadani, E.A., Radzi, S.M. 2016. Metal cation exchanged montmorillonite K10 (MMT K10 ): Surface properties and catalytic activity, Journal of Scientific Research and Development, 3, 90–96.
20. [20] Banerjee, A., Qi, J., Gogoi, R., Wong, J., Mitragotri, S. 2016. Role of nanoparticle size, shape and surface chemistry in oral drug delivery. Journal of Controlled Release, 238, 176–185.
21. [21] Jain, A., Singh, S.K., Arya, S.K., Kundu, S.C., Kapoor, S. 2018. Protein Nanoparticles: Promising Platforms for Drug Delivery Applications, ACS Biomaterial Science and Engineering, 4, 3939–3961.
22. [22] Ghosh, P., Bag, S., Roy, S.A., Subramani, E., Chaudhury, K., Dasgupta, S. 2016. Solubility enhancement of morin and epicatechin through encapsulation in an albumin based nanoparticulate system and their anticancer activity against the MDA-MB-468 breast cancer cell line. RSC Advances, 6, 101415–101429.
23. [23] Shahabadi, N., Fili, S.M., Kashanian, S. 2018. Human serum albumin interaction studies of a new copper (II) complex containing ceftobiprole drug using molecular modeling and multispectroscopic methods. Journal of Coordination Chemistry, 71, 329–341.
24. [24] Zhou, S.M., Ma, D.K., Zhang, S.H., Wang, W., Chen, W., Huang, S.M., Yu, K. 2016. PEGylated Cu3BiS3 hollow nanospheres as a new photothermal agent for 980 nm-laser-driven photothermochemotherapy and a contrast agent for X-ray computed tomography imaging. Nanoscale, 8, 1374–1382.
25. [25] Cho, K.Y., Moon, J.Y., Lee, Y.W., Lee, K.G., Yeo, J.H., Kweon, H.Y., Kim, K.H., Cho, C.S. 2003. Preparation of self-assembled silk sericin nanoparticles, International Journal of Biological Macromolecules, 32, 36–42.
26. [26] Suktham, K., Koobkokkruad, T., Wutikhun, T., Surassmo, S. 2018. Efficiency of resveratrol-loaded sericin nanoparticles: Promising bionanocarriers for drug delivery, International Journal of Pharmacology, 537, 48–56.
27. [27] Wu, J.H., Wang, Z., Xu, S.Y. 2007. Preparation and characterization of sericin powder extracted from silk industry wastewater. Food Chemistry, 103, 1255–1262.
28. [28] Wu, S., Zhao, X., Li, Y., Du, Q., Sun, J., Wang, Y., Wang, X., Xia, Y., Wang, Z., Xia, L. 2013. Adsorption Properties of Doxorubicin Hydrochloride onto Graphene Oxide: Equilibrium, Kinetic and Thermodynamic Studies. Materials (Basel). 6, 2026–2042.
29. [29] Victor, S.P., Paul, W., Jayabalan, M., Sharma, C.P. 2014. Supramolecular hydroxyapatite complexes as theranostic near-infrared luminescent drug carriers, CrystEngComm. 16, 9033–9042.
30. [30] Pradhan, N., Rajkhowa, H., Giri, H., Shrestha, B. 2015. Simultaneous spectrophotometric estimation of moxifloxacin hydrochloride and doxorubicin hydrochloride. International Journal of Pharmacy and Pharmaceutical Sciences, 7, 21–26.
31. [31] Vasić, M.V., Pezo, L., Zdravković, J.D., Bačkalić, Z., Radojević, Z. 2017. The study of thermal behavior of montmorillonite and hydromica brick clays in predicting tunnel kiln firing curve. Construction and Building Materials, 150, 872–879.
32. [32] Zauner, W., Farrow, N.A., Haines, A.M. 2001. In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density., Journal of Controlled Release, 71, 39–51.
33. [33] Jung, T., Kamm, W., Breitenbach, A., Kaiserling, E., Xiao, J.X., Kissel, T. 2000. Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake?. European Journal of Pharmaceutics and Biopharmaceutics , 50, 147–160.
34. [34] Lorenz, M.R., Holzapfel, V., Musyanovych, A., Nothelfer, K., Walther, P., Frank, H., Landfester, K., Schrezenmeier, H., Mailander, V. 2006. Uptake of functionalized, fluorescent-labeled polymeric particles in different cell lines and stem cells., Biomaterials, 27, 2820–2828. [35] Niu, G., Cogburn, B., Hughes, J. 2010. Preparation and characterization of doxorubicin liposomes. Methods in Molecular Biology, 624, 211–219.
35. [36] Yue, P.F., Lu, X.Y., Zhang, Z.Z., Yuan, H.L., Zhu, W.F., Zheng, Q., Yang, M. 2009. The study on the entrapment efficiency and in vitro release of puerarin submicron emulsion. AAPS PharmSciTech, 10, 376–383.
36. [37] Hua, S., Yang, H., Wang, W., Wang, A. 2010. Controlled release of ofloxacin from chitosan-montmorillonite hydrogel. Applied Clay Science, 50, 112–117.
37. [38] Fomi, F., Iannuccelli, V., Coppi, G., Bernabei, M.T. 1989. Effect of Montmorillonite on Drug Release from Polymeric Matrices. Archiv der Pharmazie, 793, 789–793.
38. [39] Lee, W., Jou, L. 2004. Effect of the Intercalation Agent Content of Montmorillonite on the Swelling Behavior and Drug Release Behavior of Nanocomposite Hydrogels, Journal of Applied Polymer Science, 94, 74–85.
39. [40] Elsadek, B., Kratz, F. 2012. Impact of albumin on drug delivery - New applications on the horizon. Journal of Controlled Release, 157, 4–28.
40. [41] Wang, S., Konorev, E. A., Kotamraju, S., Joseph, J., Kalivendi, S., Kalyanaraman, B. 2004. Doxorubicin Induces Apoptosis in Normal and Tumor Cells via Distinctly Different Mechanisms. Journal of Biological Chemistry, 279, 25535-25543.
41. [42] Asadishad, B., Vossoughi M., Alamzadeh, I. 2010. In vitro release behavior and cytotoxicity of doxorubicin-loaded gold nanoparticles in cancerous cells. Biotechnology Letters, 32, 649–654.