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ArticlePharmaceutical research2026

Continuous Microfluidic Manufacture of Nano-in-Microparticles Combining 3D-Printed Micromixers and Spray Drying.

Aytug Kara, Baris Ongoren, Brayan J Anaya, Aikaterini Lalatsa, Dolores R Serrano

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Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Aytug KaraDepartment of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain.
Baris OngorenDepartment of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain.
Brayan J AnayaDepartment of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain.
Aikaterini LalatsaStrathclyde Pharma Solutions, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Robertson Wing, 161 Cathedral Street, Glasgow, G4 0RE, Scotland, UK. aikaterini.lalatsa@strath.ac.uk.
Dolores R SerranoDepartment of Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, 28040, Madrid, Spain. drserran@ucm.es.ORCID http://orcid.org/0000-0002-0475-8420

Funding

Ministerio de Ciencia e Innovación PID2024-156769OB-I00Universidad Complutense de Madrid 971089
6 · The paper itself

Abstract

purposeConventional nanoparticle manufacturing techniques remain costly, labor-intensive, and difficult to scale, while also being subject to batch-to-batch variability. These limitations hinder their clinical translation, particularly in first-in-human trials. Emerging transformative technologies such as microfluidics and three-dimensional (3D) printing offer opportunities to develop agile, continuous, and scalable manufacturing processes. This study aims to demonstrate the feasibility of continuous microfluidic production of nanoparticles using customizable 3D-printed chips, integrated with atomization technologies, to generate solid nano-enabled controlled release therapies.

methods3D-printed microfluidic chips were designed using computational fluid dynamics (CFD) to optimize flow characteristics. Nifedipine (NFD)-loaded nanoparticles were continuously manufactured with Eudragit L-100 and subsequently embedded into pullulan microparticles by spray-drying, yielding nano-in-microparticles (NIM). Particle size, encapsulation efficiency, solid-state properties, permeability, and release kinetics were assessed in ex vivo Franz cell studies across porcine intestinal membranes.

resultsContinuous microfluidic processing produced NFD-loaded nanoparticles with 95% encapsulation efficiency. Spray-drying yielded spherical pullulan-based NIMs of ~ 10 µm, which, upon rehydration, released NFD nanoparticles of ~ 100 nm. The nanoparticles retained their amorphous state and displayed a three-fold increase in intestinal permeability compared to free drug, accompanied by a three-fold reduction in lag time. Release studies demonstrated reduced burst release and a sustained zero-order release profile over 24 h, favorable for blood pressure maintenance therapy.

conclusionsThe integration of 3D-printed microfluidic chip design with continuous manufacturing and spray-drying enables scalable production of solid nano-enabled therapies. The NFD-loaded NIMs demonstrated enhanced permeability and controlled release, supporting the potential of this platform for the clinical translation of nanomedicines.

Indexed as

MicrofluidicsNanoparticlesNifedipinePrinting, Three-DimensionalAnimalsDelayed-Action PreparationsDrug CompoundingDrug LiberationGlucansParticle SizePermeabilityPolymethacrylic AcidsSpray DryingSwineDelayed-Action PreparationsGlucansmethylmethacrylate-methacrylic acid copolymerNifedipinePolymethacrylic Acidspullulan3D-printed micromixerscontinuous manufacturingeudragit L-100microfluidicsmicroparticlesnano-in-microparticlesnanomedicinesnifedipinepolymeric nanoparticlesprocess intensificationspray-drying

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.