■基于脂质的纳米颗粒(LNP)因其在药物输送方面的潜力而日益受到认可,提供保护疏水性药物免受降解。LNP的工业合成,例如辉瑞-BioNTech和ModernamRNA疫苗,利用流动化学或微流体,展示其可扩展性。本研究探索了一种新型设计反应堆的利用,涡流管反应器,在LNP合成的流动化学中,旨在优化其条件,并将其与分批合成进行比较。
■使用涡流管反应器合成LNP,在水相中掺入牛血清白蛋白(BSA)作为模型药物,与有机相中的1.2-二棕榈酰基-sn-甘油-3-磷酸胆碱(DPPC)和胆固醇一起。实验设计(DoE),特别是Box-Behnken设计,用于优化参数,包括X1:流量比(10-100mL/min),X2:水与有机的体积比(1:1-10:1),和X3:反应器单元的数量(1-5个单元)。评估的反应包括物理性质和生产力。通过使粒径(Y1)最小化来确定优化条件,多分散指数(Y2),和zeta电位(Y3),在最大化截留效率(Y4)的同时,载药量(Y5),和生产率(Y5)。
■结果表明,在X1为100mL/min时达到了最佳条件,X2为5.278,X3为1个单元。在这些条件下合成的LNP表现出良好的物理性质和生产率,在批次之间保持均匀性。涡流管反应器显示出优于间歇合成的优势,产生较小的颗粒(166.23±0.98nm),更均匀的纳米颗粒(PDI0.17±0.01),和更高的截留率(67.75±1.55%)和负载能力(36.39±0.83%),表明生产率提高(313.4±12.88mg/min)。
■这项研究阐明了流动化学的潜力,特别是利用涡流管反应器,对于大规模LNP配方,提供参数关系的见解和推进纳米粒子合成的药物递送应用。
UNASSIGNED: Lipid-based nanoparticles (LNPs) is increasingly recognized for their potential in drug delivery, offering protection to hydrophobic drugs from degradation. Industrial synthesis of LNPs, exemplified by Pfizer-BioNTech and Moderna mRNA vaccines, utilizes flow chemistry or microfluidics, showcasing its scalability. This study explores the utilization of a novel design reactor, the vortex tube reactor, within flow chemistry for LNPs synthesis, aiming to optimize its conditions and compare them with batch synthesis.
UNASSIGNED: LNPs were synthesized using the vortex tube reactor, incorporating bovine serum albumin (BSA) as a model drug in the aqueous phase, alongside 1.2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol in the organic phase. Design of experiments (DoE), specifically Box-Behnken design, was employed to optimize parameters, including X1: the flow rate ratio (10-100 mL/min), X2: the aqueous-to-organic volumetric ratio (1:1-10:1), and X3: the number of reactor units (1-5 units). Responses evaluated encompassed physical properties and productivity. Optimized conditions were determined by minimizing particle size (Y1), polydispersity index (Y2), and zeta potential (Y3), while maximizing entrapment efficiency (Y4), drug loading (Y5), and productivity (Y5).
UNASSIGNED: Results indicated that optimal conditions were achieved at X1 of 100 mL/min, X2 of 5.278, and X3 of 1 unit. LNPs synthesized under these conditions exhibited favorable physical properties and productivity, with uniformity maintained across batches. The vortex tube reactor demonstrated superiority over batch synthesis, yielding smaller particles (166.23 ± 0.98 nm), more uniform nanoparticles (PDI 0.17 ± 0.01), and higher entrapment (67.75 ± 1.55%) and loading capacities (36.39 ± 0.83%), indicative of enhanced productivity (313.4 ± 12.88 mg/min).
UNASSIGNED: This study elucidates the potential of flow chemistry, particularly utilizing the vortex tube reactor, for large-scale LNPs formulation, offering insights into parameter relationships and advancing nanoparticle synthesis for drug delivery applications.