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engineered to optimize nanoparticle synthesis through fine-tuned manipulation of fluid
dynamics, mixing efficiency, and interfacial phenomena. These platforms have
facilitated the development of diverse nanodelivery systems, such as lipid nanoparticles
(LNPs), polymeric nanocarriers, and inorganic hybrids, tailored for applications in drug
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delivery, diagnostics, and theranostics (Figure 5A) . However, challenges persist in
achieving large-scale production, ensuring long-term stability, and addressing
biocompatibility concerns. Furthermore, the integration of smart materials, AI-driven
optimization, and modular microfluidic architecture presents promising avenues to
overcome these limitations and advances next-generation nanomedicine.
Bevacizumab (Bev), a humanized anti-VEGF monoclonal antibody, inhibits
malignant cell proliferation/metastasis by suppressing tumor vasculature formation and
is clinically approved for angiogenesis inhibition and cancer treatment 100 . However,
poor biodistribution and pharmacokinetics limit its bioavailability at tumor sites,
reducing efficacy 101 . Microfluidics addresses this by generating size-uniform
microgels encapsulating proteins as effective drug carriers. Chen et al. 102 developed
microgels with tumor adhesive properties and pH-dependent degradability via
microfluidics and photopolymerization for sustained local delivery of Bev/docetaxel
(DTX). This normalized tumor vasculature, enabling uniform drug distribution and
deeper penetration, improving chemotherapy outcomes and offering a platform for
treating recurrent/metastatic cancers. Huang et al. 103 prepared small, traceable,
endosome-disrupting, and bioresponsive nanogels via microfluidics for CD44-targeted
cytoplasmic delivery of therapeutic proteins (Figure 5B). Arduino et al. 104 developed
a biomimetic liposome system based on microfluidic technology and 3D printing,
overcoming blood-brain barrier penetration and immune clearance challenges in
glioblastoma treatment, enhancing PTX/carboplatin targeting and efficacy. This system
offers precise control over nanoparticle synthesis and enabling the development of
tailored nanocarriers for targeted central nervous system malignancies therapeutics.
Building on this, they developed iRGD-functionalized paclitaxel-loaded solid lipid
nanoparticles via microfluidic technology, enhancing their anticancer potential through
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