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用于生产聚乳酸-羟基乙酸共聚物纳米颗粒的微流控辅助制造工艺的开发与优化。

Development and optimization of microfluidic assisted manufacturing process to produce PLGA nanoparticles.

作者信息

Chiesa Enrica, Bellotti Marco, Caimi Alessandro, Conti Bice, Dorati Rossella, Conti Michele, Genta Ida, Auricchio Ferdinando

机构信息

Department of Surgery, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.

Department of Civil Engineering and Architecture, Via Ferrata 3, Pavia, Italy.

出版信息

Int J Pharm. 2022 Dec 15;629:122368. doi: 10.1016/j.ijpharm.2022.122368. Epub 2022 Nov 4.

Abstract

Nanomedicine consists in the application of nanotechnology in medicine to revolutionize the healthcare sector through transformative new diagnostic and therapeutic tools. In this field, nanostructures or nanocarriers (i.e., nanoparticles) are extensively used as a drug delivery system. Despite the well-defined profits offered by nanomedicines based on poly (lactic-co-glycolic acid) (PLGA), the major barriers hampering the launch of a nanoparticles-based product on the market are batch-to-batch variations and its lack of reproducibility from the benchtop to an industrial scale production. Currently, microfluidics technology has emerged as potential tool to achieve a continuous manufacturing with a precise control over fluids mixing and particles quality attributes. This work aims at defining a tailored strategy to produce PLGA NPs, exploiting a new microfluidic device. Moreover, Design of Experiments (DoE) and computational fluid dynamics approaches were exploited to understand the main process parameters and material attributes affecting the quality of the final product as well as the NPs manufacturing process. Finally, the ability to incorporate a drug into the PLGA nanoparticles was investigated by using Curcumin as model payload reaching encapsulation efficiency in the rank 28-44%. This paper is proposed as useful guide for the preparation of PLGA NPs by microfluidic technique.

摘要

纳米医学是指将纳米技术应用于医学领域,通过变革性的新型诊断和治疗工具来彻底改变医疗保健行业。在该领域,纳米结构或纳米载体(即纳米颗粒)被广泛用作药物递送系统。尽管基于聚乳酸-乙醇酸共聚物(PLGA)的纳米药物有着明确的优势,但阻碍基于纳米颗粒的产品推向市场的主要障碍是批次间差异以及从实验室规模到工业规模生产缺乏可重复性。目前,微流控技术已成为一种潜在工具,可实现连续制造,并精确控制流体混合和颗粒质量属性。这项工作旨在利用一种新型微流控装置,确定一种定制策略来生产PLGA纳米颗粒。此外,还利用实验设计(DoE)和计算流体动力学方法来了解影响最终产品质量以及纳米颗粒制造过程的主要工艺参数和材料属性。最后,以姜黄素作为模型载药,研究了将药物掺入PLGA纳米颗粒的能力,包封效率达到28%-44%。本文旨在为通过微流控技术制备PLGA纳米颗粒提供有用的指导。

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