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Tangential fiow filtration (TFF) is a purification method commonly used in a multitude of fields,including particle engineering.Currently,there is still a lack of comprehensive understanding of the effects of key TFF parameters on nanoparticle (NP) characteristics (purification outcomes).The present study aimed to investigate the influence of various factors on the characteristics of TFF-purified NP.The most commonly used NP purification method,centrifugation,was studied as a control.A design of experiment approach was implemented to investigate the influence of transmembrane pressure,flow rate,and initial drug loading on NP characteristics using paclitaxel as a model small molecule.Following the determination of optimized TFF parameters,the two purification methods were assessed using other model small molecules (i.e.tacrolimus and resveratrol).The results indicated that the TFF parameters and initial loading of the drug played important roles in the purified NP outcomes.Compared with the centrifugation method,TFF resulted in smaller NP with higher drug loading.TFF was able to circumvent issues associated with conventional centrifugation,while yielding similar results,and can potentially serve as a suitable large-scale purification method for polymeric NP.