Production of PLGA Nanoparticles via Nanoprecipitation: A Systemic Study on Synthesis Conditions

doi:10.1007/s40242-025-5042-8

高等学校化学研究 ›› 2025, Vol. 41 ›› Issue (3): 643-654.doi: 10.1007/s40242-025-5042-8

• Articles • 上一篇

Production of PLGA Nanoparticles via Nanoprecipitation: A Systemic Study on Synthesis Conditions

WEI Yushuang², XU Fengdan¹, XU Rong^2,3, LI Xiangyang², YAN Yang², LONG Rui¹, LI Ning¹, YUAN Bing²

1. Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan 523325, P. R. China;
2. Songshan Lake Materials Laboratory, Dongguan 523808, P. R. China;
3. National Laboratory of Solid State Microstructures, Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China

收稿日期:2025-03-14 修回日期:2025-04-08 出版日期:2025-06-01 发布日期:2025-05-27
通讯作者: WEI Yushuang,E-mail:weiyushuang@sslab.org.cn;LI Ning,E-mail:ningli@gdmu.edu.cn;YUAN Bing,E-mail:yuanbing@sslab.org.cn E-mail:weiyushuang@sslab.org.cn;ningli@gdmu.edu.cn;yuanbing@sslab.org.cn
基金资助:
This work was supported by the Guangdong Basic and Applied Basic Research Foundation, China (Nos. 2022A1515140063, 2024A1515012453, 2023A1515011610 and 2023B1515120001), the National Natural Science Foundation of China (Nos. 12274307, 32230063 and 12347102), the Guangdong Education Department 2023 Specialized Innovation Project (Natural Science), China (No. 2023KTSCX357), and the Dongguan Science and Technology of Social Development Program, China (No. 20231800939962).

Production of PLGA Nanoparticles via Nanoprecipitation: A Systemic Study on Synthesis Conditions

WEI Yushuang², XU Fengdan¹, XU Rong^2,3, LI Xiangyang², YAN Yang², LONG Rui¹, LI Ning¹, YUAN Bing²

1. Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, Dongguan 523325, P. R. China;
2. Songshan Lake Materials Laboratory, Dongguan 523808, P. R. China;
3. National Laboratory of Solid State Microstructures, Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, P. R. China

Received:2025-03-14 Revised:2025-04-08 Online:2025-06-01 Published:2025-05-27
Contact: WEI Yushuang,E-mail:weiyushuang@sslab.org.cn;LI Ning,E-mail:ningli@gdmu.edu.cn;YUAN Bing,E-mail:yuanbing@sslab.org.cn E-mail:weiyushuang@sslab.org.cn;ningli@gdmu.edu.cn;yuanbing@sslab.org.cn
Supported by:
This work was supported by the Guangdong Basic and Applied Basic Research Foundation, China (Nos. 2022A1515140063, 2024A1515012453, 2023A1515011610 and 2023B1515120001), the National Natural Science Foundation of China (Nos. 12274307, 32230063 and 12347102), the Guangdong Education Department 2023 Specialized Innovation Project (Natural Science), China (No. 2023KTSCX357), and the Dongguan Science and Technology of Social Development Program, China (No. 20231800939962).

摘要/Abstract

摘要： Poly(lactic-co-glycolic acid) (PLGA)-based nanomedicines exhibit significant potential for biomedical applications. Despite the approval and clinical use of PLGA microparticle products, no PLGA nanomedicine is currently available due to challenges including scaling up production. Nanoprecipitation is a one-step method with simplicity and efficiency that is capable of scaling up. However, studies on the preparation of PLGA nanoparticles (NPs) via nanoprecipitation exhibit significant variability in synthesis conditions, leading to inconsistencies in NP properties. Herein, we systematically evaluated the factors influencing the preparation of PLGA NPs through nanoprecipitation. Our results indicate that a rapid bolus injection of PLGA into aqueous solution with vigorous stirring yields smaller NPs (e.g., 125 nm with bolus versus 190 nm with 0.05 mL/min dropwise, 75 nm at 1500 r/min versus 106 nm at 100 r/min). Besides, low-concentration PLGA solutions, low ion concentrations, alkaline pH aqueous solutions, water-miscible solvents capable of dissolving PLGA, and carboxyl-terminated low molecular weight PLGA are beneficial for synthesizing NPs with smaller sizes. Importantly, this method was successfully scaled up to 1 L while maintaining consistent NP properties. The consistency, reproducibility, and scalability of this optimized method provide valuable guidance for the design and preparation of PLGA NPs, potentially facilitating their industrial production and clinical translation.

关键词: Poly(lactic-co-glycolic acid) (PLGA) nanoparticle, Nanoparticle synthesis, Nanoprecipitation

Abstract: Poly(lactic-co-glycolic acid) (PLGA)-based nanomedicines exhibit significant potential for biomedical applications. Despite the approval and clinical use of PLGA microparticle products, no PLGA nanomedicine is currently available due to challenges including scaling up production. Nanoprecipitation is a one-step method with simplicity and efficiency that is capable of scaling up. However, studies on the preparation of PLGA nanoparticles (NPs) via nanoprecipitation exhibit significant variability in synthesis conditions, leading to inconsistencies in NP properties. Herein, we systematically evaluated the factors influencing the preparation of PLGA NPs through nanoprecipitation. Our results indicate that a rapid bolus injection of PLGA into aqueous solution with vigorous stirring yields smaller NPs (e.g., 125 nm with bolus versus 190 nm with 0.05 mL/min dropwise, 75 nm at 1500 r/min versus 106 nm at 100 r/min). Besides, low-concentration PLGA solutions, low ion concentrations, alkaline pH aqueous solutions, water-miscible solvents capable of dissolving PLGA, and carboxyl-terminated low molecular weight PLGA are beneficial for synthesizing NPs with smaller sizes. Importantly, this method was successfully scaled up to 1 L while maintaining consistent NP properties. The consistency, reproducibility, and scalability of this optimized method provide valuable guidance for the design and preparation of PLGA NPs, potentially facilitating their industrial production and clinical translation.

Key words: Poly(lactic-co-glycolic acid) (PLGA) nanoparticle, Nanoparticle synthesis, Nanoprecipitation

WEI Yushuang, XU Fengdan, XU Rong, LI Xiangyang, YAN Yang, LONG Rui, LI Ning, YUAN Bing. Production of PLGA Nanoparticles via Nanoprecipitation: A Systemic Study on Synthesis Conditions[J]. 高等学校化学研究, 2025, 41(3): 643-654.

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Production of PLGA Nanoparticles via Nanoprecipitation: A Systemic Study on Synthesis Conditions

Production of PLGA Nanoparticles via Nanoprecipitation: A Systemic Study on Synthesis Conditions

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