Abstract
Doxorubicin(DOX)-loaded chitosan oligosaccharide(CSO)/indomethacin(Indo) nanoparticles(NPs) was developed as a uniform particle size, high drug loaded capacity, good biostability and biocompatibility drug delivery system. According to the principle of “Like dissolves like”, Indo was grafted to the bones of CSO under mild condition. The CSO/Indo NPs were formed by ultrasonic dispersion method in the aqueous medium. The critical aggregation concentrations of the CSO/Indo NPs were from 33.89 µg/ml to 287.92 µg/ml. The IC50 of blank CSO/Indo NPs (311.06 µg/ml–1365.3 µg/ml) on HepG2 cell lines indicated that they could be used as safe carriers except CSO18000/Indo100%. DOX–loaded NPs were prepared by a dialysis method. The sizes of drug-loaded NPs were significantly smaller than those of the corresponding blank nanoparticles while all the zeta potentials of drug-loaded nanoparticles were lower than those blank nanoparticles. These data supported our original scientific hypothesis that the π bonds in the structure of CSO/Indo might generate the physical interaction with the π bonds of DOX. Compared with the IC50 of free DOX·HCl solution (8.576 µg/ml), the IC50 of the drug-loaded NPs (3.125 µg/ml—4.524 µg/ml) showed that they had obvious enhanced anti-tumour effect. Therefore, CSO/Indo NPs provided a new choice for insoluble anticancer drugs.
Graphic Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jaime Feliu, Victoria Heredia-Soto, Regina Gironés, et al. (2018). Can we avoid the toxicity of chemotherapy in elderly cancer patients? Critical Reviews in Oncology/Hematology 131, 16–23.
M. Sarwar Hossen, M. K. Khalid Hossain, et al. (2019). Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies A review. Journal of Advanced Research 15, 1–18.
Xu. Qing, Yuexian Liu, Su. Shishuai, Wei Li, Chunying Chen, and Wu. Yan (2012). Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles. Biomaterials 33 (5), 1627–1639.
Kwangmeyung Kim (2010). Jong Ho Kim, Hyungkyu Park, Yoo-Shin Kim, Kyeongsoon Park, Heayun Nam, Seulki Lee, Jae Hyung Park, Rang-Woon Park, In-San Kim, Kuiwon Choi, Sang Yoon Kim, Kinam Park, Ick Chan Kwon. Tumor-homing multifunctional nanoparticles for cancer theragnosis: Simultaneous diagnosis, drug delivery, and therapeutic monitoring Journal of Controlled Release 146 (2), 219–227.
Gan Liu, Hongjun Gao, Yixiong Zuo, Xiaowei Zeng, Wei Tao, Hsiang-i Tsai, and Lin Mei (2017). DACHPt-loaded unimolecular micelles based on hydrophilic dendritic block copolymers for enhanced therapy of lung cancer ACS appl. Mater. & Interfaces 9, 112–119.
Gan Liu, Hsiang-i Tsai, Xiaowei Zeng, Yixiong Zuo, Wei Tao, Jun Han, and Lin Mei (2017). Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression. Theranostics 7 (5), 1192–1203.
Gan Liu, Hsiang-I. Tsai, Xiaowei Zeng, Junyang Qi, Miaomiao Luo, Xusheng Wang, Lin Mei, and Wenbin Deng (2019). Black phosphorus nanosheets-based stable drug delivery system via drugself-stabilization for combined photothermal and chemo cancer therapy. Chemical Engineering Journal 375 (121917), 1–10.
T. Kean (2010). Thanou Biodegradation, biodistribution and toxicity of chitosan. Advanced Drug Delivery Reviews 62 (1), 3–11.
X. H. Wei, Y. P. Niu, Y. Y. Xu, et al. (2010). Salicylic acid-grafted chitosan oligosaccharide nanoparticle for paclitaxel delivery. Journal of Bioactive and Compatible Polymer. 25 (3), 319–335.
B. S. Andres and E. K. Martina (1998). Mucoadhesive polymers as platforms for peroral peptide delibery and absorption: synthesis and evalution of different chitosan—EDTA conjugates. Journal Controlled Release 50 (2–3), 215–223.
M. Morimoto, A. Hashidzume, Y. Morishima, et al. (2003). Fluorescence studies of associative behavior of cationic surfactant moieties covalently linked to poly ( acrylamide) at the surfactant head or tail. Polymer 44 (4), 943.
R. B. Sashidhar, A. K. Capoor, and D. Ramana (1994). Quantitation of ∈-amino group using amino acids as reference standards by trinitrobenzene sulfonic acid A simple spectrophotometric method for the estimation of hapten to carrier protein ratio. Journal of Immunological Methods 167 (1–23), 121–127.
Mingyan Yan, Bafang Li, and Xue Zhao (2010). Food Chemistry 122 (415), 1333–1337.
J DUHAMEL Pyrene fluorescence to study polymeric systems. In Molecular Interfacial Phenomena of Polymers and Biopolymers. Book chapter 7. 2005, 214–248.
A. Rahman and C. W. Brown (2003). Effect of pH on the critical micelle concentration of sodium dodecyl sulphate. Journal of Applied Polymer Science 28 (4), 1331–1334.
J. P. Kratohvil, W. P. Hsu, and V. Kwok (1986). How large are the micelles of di-a-hydroxy bile salts at the critical micellization concentrations in aqueous electrolyte solutions? Results for sodium taurodeoxycholate and sodium deoxycholate. Langmuir 2, 256–258.
Z. Tong, W. Luo, Y. Wang, et al. (2010). Tumor tissue-derived formaldehyde and acidic microenvironment synergisticallyinduce bone cancer pain. PLoS One. 5 (4), 10234.
Acknowledgements
We would like to thank National Natural Science Foundation of China (30973683) and Natural Science Foundation of Zhejiang Province (Y2090477 and LY14H300006) for their financial support.
Author information
Authors and Affiliations
Contributions
Conceptualization: X-HW, Methodology: X-HW, Formal Analysis: X-HW, Investigation: P-WH, X-HW, Resources: X-HW, S-LS, WZ, HW, Data Curation: X-HW, Writing – Original Draft Preparation, P-WH, X-HW, Writing – Review & Editing, X-HW, P-WH, Z-WZ, Supervision: X-HW, Project Administration: X-HW; Funding Acquisition: X-HW.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Research Involving Human Participants and/or Animals
The animal experiment program in the article strictly abided by the national and Zhejiang province’s laboratory animal welfare ethics and protection regulations, complied with the “Guiding Opinions on the Good Treatment of Laboratory Animals” and other regulations of the Ministry of Science and Technology, China.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Huang, PW., Zeng, ZW., Zheng, W. et al. Synthesis, Preparation and Evaluation of Doxorubicin-Loaded Chitosan Oligosaccharide/Indomethacin Nanoparticles. J Clust Sci 33, 795–808 (2022). https://doi.org/10.1007/s10876-021-02017-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10876-021-02017-4