Abstract

Nanoparticles (NPs) have found a wide range of applications in clinical therapeutic and diagnostic fields. However, currently most NPs are still in the preclinical evaluation phase with few approved for clinical use. Microfluidic systems can simulate dynamic fluid flows, chemical gradients, partitioning of multi-organs as well as local microenvironment controls, offering an efficient and cost-effective opportunity to fast screen NPs in physiologically relevant conditions. Here, in this review, we are focusing on summarizing key microfluidic platforms promising to mimic in vivo situations and test the performance of fabricated nanoparticles. Firstly, we summarize the key evaluation parameters of NPs which can affect their delivery efficacy, followed by highlighting the importance of microfluidic-based NP evaluation. Next, we will summarize main microfluidic systems effective in evaluating NP haemocompatibility, transport, uptake and toxicity, targeted accumulation and general efficacy respectively, and discuss the future directions for NP evaluation in microfluidic systems. The combination of nanoparticles and microfluidic technologies could greatly facilitate the development of drug delivery strategies and provide novel treatments and diagnostic techniques for clinically challenging diseases.

Highlights

  • With recent advances in nanotechnology, a variety of nanoparticles (NPs) have been fabricated, including liposomes [1,2], gold and silver NPs [3,4], polymeric micelles [5], magnetic NPs [6,7], quantum dots [8,9] and so on

  • Despite the fact that several NPs have already been approved for clinical cancer treatment by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including AbraxaneTM, DoxilTM and gold nanoshellsTM [20], more NPs are still in the preclinical evaluation phase

  • Based on its general features, single-cell culture models, complicated 3D tumor cultures and various organs-on-chip models are developed in microfluidic devices [3,69,70,71,72]

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Summary

Introduction

With recent advances in nanotechnology, a variety of nanoparticles (NPs) have been fabricated, including liposomes [1,2], gold and silver NPs [3,4], polymeric micelles [5], magnetic NPs [6,7], quantum dots [8,9] and so on. The 3D cell culture models such as tumor spheroids could mimic complex tissue structures to a certain extent, but failed to mimic the existence of chemical gradients and flow conditions As a result, both 2D and 3D cell culture platforms could reach unmatched testing results compared with in vivo [21]. The patient-dependent phenotypes of biotissues and the heterogeneity of biosamples within the same patient further increase the optimization difficulty [24] With these challenges mentioned above, better NP testing platforms which could evaluate NPs under physiologically relevant conditions and provide patient-dependent characterizations which are highly needed. Microfluidic systems can simulate dynamic fluid flows, chemical gradients, partitioning of multi-organs as well as local microenvironment controls, offering an efficient and cost-effective opportunity to fast screen NPs in terms of transport and efficacy for multiple clinical applications [21]. The challenges and future directions of the development of microfluidic systems for NP evaluation are discussed

Key Evaluation Parameters of NP Efficacy Testing for Drug Delivery
Positioning of Microfluidic Systems in NP Performance Evaluation
Key Microfluidic Models for NP Evaluation
NP Haemocompatibility
NP Transport
NP Accumulation in Target Tissue
NP Efficacy
Findings
Discussion

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