Biosensors and Nanotheranostics

Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110986

Submitted: 29 April 2026 Revised: 14 June 2026  Accepted: 25 June 2026  Published: 27 June 2026 


Abstract

Liposomes remain the most clinically validated class of nanocarriers, yet the step that most often decides whether a promising theranostic formulation ever reaches patients is not its design but its manufacture. Conventional bulk methods, such as thin-film hydration and ethanol injection, rely on chaotic macroscale mixing that yields polydisperse, frequently multilamellar vesicles and demands harsh post-processing, leaving a batch-to-batch variability that is difficult to reconcile with Good Manufacturing Practice (GMP). This review examines how microfluidic continuous-flow manufacturing has reframed that problem. Operating within sub-millimetre channels under laminar, diffusion-dominated flow, microfluidic platforms assemble size-tunable (approximately 20 to 200 nm), narrowly dispersed (PDI < 0.2) small unilamellar vesicles in a single step, with critical quality attributes governed predictably by the flow rate ratio and total flow rate. We synthesize evidence that this control translates into theranostic performance: two- to three-fold higher loading of hydrophobic photosensitizers and metallic nanoparticles, cleaner co-encapsulation of multi-modal cargoes such as doxorubicin with gadolinium chelates, gold nanorods, or iron oxide, and measurable gains in MRI relaxivity and triggered release. We then revisit the scale-up question long separating bench elegance from clinical supply, comparing parallelization, 3D-printed multilayer chips (up to 474 mL/min), and vortex focusing (exceeding 20 g/h) as routes to industrial throughput without surrendering monodispersity. Finally, we outline how Quality by Design and in-line Process Analytical Technology close the loop toward automated, regulation-ready production. Taken together, the literature suggests that microfluidics is maturing from a characterization tool into a credible manufacturing paradigm, even as standardization and regulatory precedent remain unfinished.

Keywords: theranostic liposomes; microfluidics; hydrodynamic flow focusing; process intensification; Quality by Design; Process Analytical Technology; co-encapsulation; GMP manufacturing.

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