Chitosan nanoparticles for sustained release of metformin and its derived synthetic biopolymer for bone regeneration

Frontiers in Bioengineering and Biotechnology

Bioengineering and Biotechnology

Yong-Bo Peng¹  Qin Ye²  Jing Hu²  Yun-Zhi Feng²  Xiao-Lin Su²  Ze-Yue Ou-Yang²  Ning-Xin Chen²  Li Tan²  Yun Chen²  Yue Guo²  Qiong Liu²  Meng-Mei Zhong²  Jie Zhao²  Ya-Qiong Zhao²  Qian Zhang²  Yao Feng²  Hui Yuan²  Marie Aimee Dusenge² 

[1] Chongqing Key Laboratory for Pharmaceutical Metabolism Research, The Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China;Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;

关键词: biopolymer;    chitosan;    metformin;    drug release;    BMSCs;    bone regeneration;   

DOI  :  10.3389/fbioe.2023.1169496

 received in 2023-02-19, accepted in 2023-06-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: There are considerable socioeconomic costs associated with bone defects, making regenerative medicine an increasingly attractive option for treating them. Chitosan is a natural biopolymer; it is used in approaches for sustained slow release and osteogenesis, and metformin has osteoinductivity. Our study aimed to synthesize chitosan and human serum albumin (HSA) with a metformin nanoformulation to evaluate the therapeutic effects of this nanoformulation on bone defects in vitro.Methods: A pluripotent differentiation assay was performed in vitro on mouse bone marrow mesenchymal stem cells (BMSCs). Cell Counting Kit-8 was used to detect whether metformin was toxic to BMSCs. The osteogenesis-related gene expression of osteocalcin (OCN) and osteoprotegerin (OPG) from BMSCs was tested by real-time polymerase chain reaction (PCR). HSA, metformin hydrochloride, and chitosan mixtures were magnetically stirred to finish the assembly of metformin/HSA/chitosan nanoparticles (MHC NPs). The MHC NPs were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). To test the expression of OCN and OPG, western blot were used. MHC NPs were evaluated in vitro for their osteoinductivity using alkaline phosphatase (ALP).Results: BMSCs successfully differentiated into osteogenic and adipogenic lineages in vitro. According to real-time PCR, a 50 µM concentration of metformin promoted osteogenesis in BMSCs most effectively by upregulating the osteogenic markers OCN and OPG. The microstructure of MHC NPs was spherical with an average nanosize of 20 ± 4.7 nm and zeta potential of −8.3 mV. A blueshift and redshift were observed in MHC NPs following exposure to wavelengths of 1,600–1,900 and 2,000–3,700 nm, respectively. The encapsulation (%) of metformin was more than 90%. The simulation study showed that MHC NPs have good stability and it could release metformin slowly in vitro at room temperature. Upon treatment with the studied MHC NPs for 3 days, ALP was significantly elevated in BMSCs. In addition, the MHC NPs-treated BMSCs upregulated the expression of OPG and OCN, as shown by real-time PCR and western blot.Conclusion: MHC NPs have a stable metformin release effect and osteogenic ability. Therefore, as a derived synthetic biopolymer, it is expected to play a role in bone tissue regeneration.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Su, Feng, Liu, Tan, Yuan, Chen, Zhao, Zhao, Dusenge, Hu, Ye, Ou-Yang, Zhong, Zhang, Guo, Feng and Peng.