Design, Characterization and in vitro Simulations of nano-HAP/GO Composite Drug Delivery System Produced by Hydrothermal Methods Loaded with Paclitaxel

Fatih Çiftçi

doi:10.17776/csj.1258573

EN

Design, Characterization and in vitro Simulations of nano-HAP/GO Composite Drug Delivery System Produced by Hydrothermal Methods Loaded with Paclitaxel

Abstract

In this study, it was aimed to develop a nano drug system that can be used in passive targeting in pancreatic cancer treatment. Hydroxyapatite nanocrystals (n-HAP) produced by hydrothermal process and graphene oxide (GO) produced by hummers method were used to increase the carrier capacity of the nano drug system and to activate the drug release kinetics and drug loading capacity. Analyses performed for nanocomposite drug carrier systems; FT-IR, XRD, TGA, BET analysis, Zeta potential, TEM and SEM. Paclitaxel (PTX), a chemotherapeutic drug used in the treatment of pancreatic cancer, was loaded into HAP nanocrystals (PTX- loaded n-HAP) and its activity on pancreatic cancer cells was investigated. When PTX was 1 and 2 mg, Encapsulation Efficiency (EE) and Drug Loading Content (LC) were 79.17-72.24% and 80.01-80.27%, respectively, for H-n-HAP crystal structure only, while EE and LC were 88.57-81.57% and 90.84-110.57%, respectively, when H-n-HAP crystal structure was loaded with 1 and 2 mg PTX together with GO. Here, it was observed PTX release profiles are according to the Hixson model. According to Fick's law, release profile was observed with values of k=1.89, n=0.21, SSD=0.04, R2=0.997, FIC=2.03, SD=0.004. In cell culture studies, as GO nanomaterials were loaded into H-n-HAP nanocrystal structure, the effect of PTX drug on pancreatic cancer increased and the viability of cancer cells decreased. It can be concluded that H-n-HAP/GO/PTX nanocomposite structure kills more pancreatic cancer cells with synergistic effect.

Keywords

Supporting Institution

Fatih Sultan Mehmet Vakıf University

Project Number

FSMVU-BAP 2022104D

References

[1] V. Andretto, A. Rosso, S. Briançon, and G. Lollo, Nanocomposite systems for precise oral delivery of drugs and biologics, Drug Deliv Transl Res., 11(2) 2021 445–470.
[2] F. Ciftci, Release kinetics modelling and in vivo-vitro, shelf-life study of resveratrol added composite transdermal scaffolds, Int J Biol Macromol., 235 (2023) 123769.
[3] S. Javanbakht and H. Namazi, Doxorubicin loaded carboxymethyl cellulose/graphene quantum dot nanocomposite hydrogel films as a potential anticancer drug delivery system, Mater Sci Eng C., 87 (2018) 50–59.
[4] M. J. Mitchell, M. M. Billingsley, R. M. Haley, M. E. Wechsler, N. A. Peppas, and R. Langer, Engineering precision nanoparticles for drug delivery, Nature Reviews Drug Discovery., 20(2) (2021) 101–124.
[5] Venkata V.V., Omathanu P.P., Nanosystems for Dermal and Transdermal Drug Delivery, in Drug Delivery Nanoparticles Formulation and Characterization., 1st Edition. CRC Press, (2020) 146–175.
[6] A. C. Özarslan, C. Özel, M. D. Okumuş, D. Doğan, and S. Yücel, Development, structural and rheological characterization, and in vitro evaluation of the zinc-doped 45S5 bioactive glass-vaseline ointment for potential wound healing applications, J Mater Res, (2023).
[7] S. Hussain and K. Sabiruddin, Synthesis of eggshell based hydroxyapatite using hydrothermal method, IOP Conf Ser Mater Sci Eng., 1189(1) (2021).
[8] H. S. Liu et al., Hydroxyapatite synthesized by a simplified hydrothermal method, Ceram Int., 23(1) (1997) 19–25.

[9] Y. P. Guo, Y. B. Yao, C. Q. Ning, Y. J. Guo, and L. F. Chu, Fabrication of mesoporous carbonated hydroxyapatite microspheres by hydrothermal method, Mater Lett., 65(14) (2011) 2205–2208.
[10] G. Zhang, J. Chen, S. Yang, Q. Yu, Z. Wang, and Q. Zhang, Preparation of amino-acid-regulated hydroxyapatite particles by hydrothermal method, Mater Lett., 65(3) (2011) 572–574.
[11] A. Razaq, F. Bibi, X. Zheng, R. Papadakis, S. H. M. Jafri, and H. Li, Review on Graphene-, Graphene Oxide-, Reduced Graphene Oxide-Based Flexible Composites: From Fabrication to Applications, Materials, (2022).
[12] A. Jiříčková, O. Jankovský, Z. Sofer, and D. Sedmidubský, Synthesis and Applications of Graphene Oxide, Materials., (2022).
[13] A. Raslan, L. Saenz del Burgo, J. Ciriza, and J. Luis Pedraz, Graphene oxide and reduced graphene oxide-based scaffolds in regenerative medicine, Int J Pharm, 580 (2020) 119226.
[14] C. Daulbayev et al., Effect of graphene oxide/hydroxyapatite nanocomposite on osteogenic differentiation and antimicrobial activity, Surfaces and Interfaces., (2022).
[15] F. Ciftci et al., Selenium and clarithromycin loaded PLA-GO composite wound dressings by electrospinning method, Int J Polym Mater Polym Biomater., (2022).
[16] M. S. Al Mogbel, M. T. Elabbasy, M. F. H. Abd El-Kader, R. S. Mohamed, M. E. Moustapha, and A. A. Menazea, Morphological, mechanical, and antibacterial investigation of a ternary nanocomposite contains hydroxyapatite, tellurium(IV) oxide (Te2O4), and graphene oxide in vitro, Appl Phys A Mater Sci Process., (2022).
[17] Z. Benzait, P. Chen, and L. Trabzon, Enhanced synthesis method of graphene oxide, Nanoscale Adv., (2021).
[18] F. Ciftci et al., Antibacterial and cellular behavior of PLA-based bacitracin and zataria multiflora nanofibers produced by electrospinning method, Int J Polym Mater Polym Biomater, 72(4) (2023) 319–334.
[19] B. Wójcik et al., Effects of metallic and carbon-based nanomaterials on human pancreatic cancer cell lines aspc-1 and bxpc-3, Int J Mol Sci., 22(2) (2021).
[20] S. S. Kim et al., Hyperthermal paclitaxel-bound albumin nanoparticles co-loaded with indocyanine green and hyaluronidase for treating pancreatic cancers, Arch Pharm Res., 44(2) (2021) 182–193.
[21] K. Lin et al., Selective laser sintered nano-HA/PDLLA composite microspheres for bone scaffolds applications, Rapid Prototyp J., (2020).
[22] Y. Chen et al., Dual Template, Three-Dimensional Hierarchical Porous Scaffolds Based on Graphene Oxide for Bone Tissue Engineering, ECS Meet Abstr., (2020).
[23] J. Prakash, D. Prema, K. S. Venkataprasanna, K. Balagangadharan, N. Selvamurugan, and G. D. Venkatasubbu, Nanocomposite chitosan film containing graphene oxide/hydroxyapatite/gold for bone tissue engineering, Int J Biol Macromol., (2020).
[24] A. C. Özarslan and S. Yücel, Comprehensive assessment of SrO and CuO co-incorporated 50S6P amorphous silicate bioactive glasses in vitro: Revealing bioactivity properties of bone graft biomaterial for bone tissue engineering applications, Ceram Int., (2023).
[25] I. P. Khosalim, Y. Y. Zhang, C. K. Y. Yiu, and H. M. Wong, Synthesis of a graphene oxide/agarose/hydroxyapatite biomaterial with the evaluation of antibacterial activity and initial cell attachment, Sci Rep., (2022).
[26] F. Miculescu et al., Considerations and Influencing Parameters in EDS Microanalysis of Biogenic Hydroxyapatite, J Funct Biomater., (2020).
[27] A. C. Özarslan, Y. B. Elalmis, and S. Yücel, Production of biosilica based bioactive glass-alginate composite putty as bone support material, and evaluation of in vitro properties; bioactivity and cytotoxicity behavior, J Non Cryst Solids, (2021).
[28] M. N. Ozder, F. Ciftci, O. Rencuzogullari, E. D. Arisan, and C. B. Ustündag, In situ synthesis and cell line studies of nano-hydroxyapatite/graphene oxide composite materials for bone support applications, Ceram Int., (2023).
[29] M. Ikram et al., Photocatalytic and antibacterial activity of graphene oxide/cellulose-doped TiO2 quantum dots: in silico molecular docking studies, Nanoscale Adv., 4(18) (2022) 3764–3776.
[30] A. Alangari et al., Antimicrobial, anticancer, and biofilm inhibition studies of highly reduced graphene oxide (HRG): In vitro and in silico analysis, Front Bioeng Biotechnol., 11 (2023).
[31] E. Peng, N. Todorova, and I. Yarovsky, Effects of Size and Functionalization on the Structure and Properties of Graphene Oxide Nanoflakes: An in Silico Investigation, ACS Omega., 3(9) (2018) 11497–11503.
[32] P. S. Gade, R. M. Sonkar, and P. Bhatt, Graphene oxide-mediated fluorescence turn-on GO-FAM-FRET aptasensor for detection of sterigmatocystin, Anal Methods., 14(39) (2022) 3890–3897.

Details

Primary Language

English

Subjects

Biomaterial , Composite and Hybrid Materials

Journal Section

Research Article

Authors

Fatih Çiftçi ^*
0000-0002-3062-2404
Türkiye

Publication Date

June 30, 2023

Submission Date

March 1, 2023

Acceptance Date

June 19, 2023

Published in Issue

Year 2023 Volume: 44 Number: 2

DOI

https://doi.org/10.17776/csj.1258573

IZ

https://izlik.org/JA83ZK47LT

Cite

RIS / Bibtex

APA

Çiftçi, F. (2023). Design, Characterization and in vitro Simulations of nano-HAP/GO Composite Drug Delivery System Produced by Hydrothermal Methods Loaded with Paclitaxel. Cumhuriyet Science Journal, 44(2), 302-314. https://doi.org/10.17776/csj.1258573