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

作者全名："Chen, Ning-Xin; Su, Xiao-Lin; Feng, Yao; Liu, Qiong; Tan, Li; Yuan, Hui; Chen, Yun; Zhao, Jie; Zhao, Ya-Qiong; Dusenge, Marie Aimee; Hu, Jing; Ye, Qin; Ou-Yang, Ze-Yue; Zhong, Meng-Mei; Zhang, Qian; Guo, Yue; Feng, Yun-Zhi; Peng, Yong-Bo"

作者地址："[Chen, Ning-Xin; Su, Xiao-Lin; Feng, Yao; Liu, Qiong; Tan, Li; Yuan, Hui; Chen, Yun; Zhao, Jie; Zhao, Ya-Qiong; Dusenge, Marie Aimee; Hu, Jing; Ye, Qin; Ou-Yang, Ze-Yue; Zhong, Meng-Mei; Zhang, Qian; Guo, Yue; Feng, Yun-Zhi] Cent South Univ, Xiangya Hosp 2, Dept Stomatol, Changsha, Hunan, Peoples R China; [Peng, Yong-Bo] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China"

通信作者："Guo, Y; Feng, YZ (通讯作者)，Cent South Univ, Xiangya Hosp 2, Dept Stomatol, Changsha, Hunan, Peoples R China.; Peng, YB (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China."

来源：FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY

ESI学科分类：Multidisciplinary

WOS号：WOS:001031846600001

JCR分区：Q1

影响因子：4.3

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

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

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 mu M 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."

基金机构："National Natural Science Foundation of China [81800788, 81773339]; Science and Technology Department of Hunan Province, China [2017WK2041, 2018SK52511, 2022ZK4084]; Scientific Research Project of Hunan Provincial Health Commission [202208043514, B202308056340]; Hunan Provincial Natural Science Foundation of China [2022JJ30062]; Natural Science Foundation of Changsha City [kq2202403, kq2202412]; Xiangya Clinical Medicine Database of Central South University [2014-ZDYZ-1-16]; Education and Teaching Reform Research Project of Central South University [2020jy165-3]; Research Project on Postgraduate Education and Teaching Reform of Central South University [2021JGB072]; Hunan Provincial Innovation Foundation For Postgraduate [CX20220370]; Fundamental Research Funds for the Central Universities of Central South University [2023ZZTS0905, 2023ZZTS0247]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (81800788 and 81773339), Science and Technology Department of Hunan Province, China (2017WK2041, 2018SK52511, and 2022ZK4084), Scientific Research Project of Hunan Provincial Health Commission (202208043514 and B202308056340), Hunan Provincial Natural Science Foundation of China (2022JJ30062), Natural Science Foundation of Changsha City (kq2202403 and kq2202412), Fund for the Xiangya Clinical Medicine Database of Central South University (2014-ZDYZ-1-16), Education and Teaching Reform Research Project of Central South University (2020jy165-3), Research Project on Postgraduate Education and Teaching Reform of Central South University (2021JGB072), Hunan Provincial Innovation Foundation For Postgraduate (CX20220370); and the Fundamental Research Funds for the Central Universities of Central South University (2023ZZTS0905 and 2023ZZTS0247)."