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Pharmaceutics
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Microfluidics in Drug Delivery
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Microfluidics in Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 25296

Special Issue Editors

Dr. Sharon Shui Yee Leung

E-Mail Website
Guest Editor
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Interests: pulmonary drug delivery; particle engineering; formulation sciences; bacteriophage; phage proteins
Dr. Megan Yi-Ping Ho

E-Mail Website
Guest Editor
Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: microfluidics; lab on a chip; nanosensor; biomateirals; DNA sensor systems

Special Issue Information

Dear Colleagues,

Microfluidics, allowing the precise control and manipulation of fluids, have emerged as powerful tools for drug delivery. In recent decades, microfluidic technologies have largely been used for the production of micro- and nanodrug carriers/drug suspensions. As more new, state-of-the-art manufacturing facilities for microfluidic devices become available, their applications rapidly expand, including local and controlled drug delivery for both small molecule drugs and biologics, drug delivery monitoring to track and analyze the therapeutic effects of drugs, and controlled dosing. Microfluidics-based drug delivery systems are creating a new revolution in drug delivery.

This Special Issue aims to collect recent advances in the microfluidic technologies developed for drug delivery. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not be limited to) the following:

  1. Wearables or implantable microdevices;
  2. Microfluidics-assisted controlled drug delivery;
  3. Microneedles;
  4. Microfluidic systems for drug delivery system production;
  5. Organs on a chip.

We look forward to receiving your contributions.

Dr. Sharon Shui Yee Leung
Dr. Megan Yi-Ping Ho
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microfluidics
  • drug delivery systems
  • smart particles
  • controlled drug delivery
  • microdevices

Published Papers (7 papers)

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Research

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12 pages, 5492 KiB  
Article
Development of In Situ Microfluidic System for Preparation of Controlled Porous Microsphere for Tissue Engineering
by Ji Hwan Han, Chul Min Kim, Tae-Hyun Kim, Songwan Jin and Gyu Man Kim
Pharmaceutics 2022, 14(11), 2345; https://doi.org/10.3390/pharmaceutics14112345 - 30 Oct 2022
Cited by 2 | Viewed by 1823
Abstract
In this study, we present an in situ microfluidic system to precisely control highly porous polycaprolactone microspheres as tissue templates for tissue engineering. The porosity of the microspheres was controlled by adjusting the flow rates of the polymer phase and the pore-generating material [...] Read more.
In this study, we present an in situ microfluidic system to precisely control highly porous polycaprolactone microspheres as tissue templates for tissue engineering. The porosity of the microspheres was controlled by adjusting the flow rates of the polymer phase and the pore-generating material phase in the dispersed phase. The microfluidic flow-focusing technique was adopted to manufacture porous microspheres using a relatively highly viscous polymer solution, and the device was fabricated by conventional photolithography and PDMS casting. The fabricated in situ microfluidic system was used to precisely control the pore size of monodispersed polycaprolactone microspheres. The porous microspheres with controlled pore sizes were evaluated by culturing HDF cells on the surface of porous microspheres and injection into the subcutaneous tissue of rats. We found that the increased pore size of the microspheres improved the initial proliferation rate of HDF cells after seeding and relieved the inflammatory response after the implantation of porous microspheres in the subcutaneous tissue of rats. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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16 pages, 5205 KiB  
Article
Preparation of Drug-Loaded Liposomes with Multi-Inlet Vortex Mixers
by Huangliang Zheng, Hai Tao, Jinzhao Wan, Kei Yan Lee, Zhanying Zheng and Sharon Shui Yee Leung
Pharmaceutics 2022, 14(6), 1223; https://doi.org/10.3390/pharmaceutics14061223 - 9 Jun 2022
Cited by 11 | Viewed by 2781
Abstract
The multi-inlet vortex mixer (MIVM) has emerged as a novel bottom-up technology for solid nanoparticle preparation. However, its performance in liposome preparation remains unknown. Here, two key process parameters (aqueous/organic flow rate ratio (FRR) and total flow rate (TFR)) of MIVM were investigated [...] Read more.
The multi-inlet vortex mixer (MIVM) has emerged as a novel bottom-up technology for solid nanoparticle preparation. However, its performance in liposome preparation remains unknown. Here, two key process parameters (aqueous/organic flow rate ratio (FRR) and total flow rate (TFR)) of MIVM were investigated for liposome preparation. For this study, two model drugs (lysozyme and erythromycin) were chosen for liposome encapsulation as the representative hydrophilic and hydrophobic drugs, respectively. In addition, two modified MIVMs, one with herringbone-patterned straight inlets and one with zigzag inlets, were designed to further improve the mixing efficiency, aiming to achieve better drug encapsulation. Data showed that FRR played an important role in liposome size control, and a size of <200 nm was achieved by FRR higher than 3:1. Moreover, increasing TFR (from 1 to 100 mL/min) could further decrease the size at a given FRR. However, similar regularities in controlling the encapsulation efficiency (EE%) were only noted in erythromycin-loaded liposomes. Modified MIVMs improved the EE% of lysozyme-loaded liposomes by 2~3 times at TFR = 40 mL/min and FRR = 3:1, which was consistent with computational fluid dynamics simulations. In summary, the good performance of MIVM in the control of particle size and EE% makes it a promising tool for liposome preparation, especially for hydrophobic drug loading, at flexible production scales. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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15 pages, 4721 KiB  
Article
Screening for Best Neuronal-Glial Differentiation Protocols of Neuralizing Agents Using a Multi-Sized Microfluidic Embryoid Body Array
by Christoph Eilenberger, Mario Rothbauer, Konstanze Brandauer, Sarah Spitz, Eva-Kathrin Ehmoser, Seta Küpcü and Peter Ertl
Pharmaceutics 2022, 14(2), 339; https://doi.org/10.3390/pharmaceutics14020339 - 31 Jan 2022
Cited by 1 | Viewed by 2282
Abstract
Stem cell technology and embryonic stem cell models are of great interest in biomedical research since they provide deeper insights into, e.g., neurogenesis and early mammalian brain development. Despite their great scientific potential, the reliable establishment of three-dimensional embryoid bodies (EBs) remains a [...] Read more.
Stem cell technology and embryonic stem cell models are of great interest in biomedical research since they provide deeper insights into, e.g., neurogenesis and early mammalian brain development. Despite their great scientific potential, the reliable establishment of three-dimensional embryoid bodies (EBs) remains a major challenge, and the current lack of standardization and comparability is still limiting a broader application and translation of stem cell technology. Among others, a vital aspect for the reliable formation of EBs is optimizing differentiation protocols since organized differentiation is influenced by soluble inducers and EB size. A microfluidic biochip array was employed to automate cell loading and optimize directed neuronal and astrocytic differentiation protocols using murine P19 embryoid bodies to facilitate reliable embryonic stem cell differentiation. Our gravity-driven microfluidic size-controlled embryoid body-on-a-chip system allows (a) the robust operation and cultivation of up to 90 EBs in parallel and (b) the reproducible generation of five increasing sizes ranging from 300 µm to 1000 µm diameters. A comparative study adds two differentiation-inducers such as retinoic acid and EC23 to size-controlled embryoid bodies to identify the optimal differentiation protocol. Our study revealed a 1.4 to 1.9-fold higher neuron and astrocyte expression in larger embryoid bodies (above 750 µm) over smaller-sized EBs (below 450 µm), thus highlighting the importance of EB size in the establishment of robust neurodevelopmental in vitro models. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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17 pages, 5652 KiB  
Article
A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies
by Behnam Noorani, Aditya Bhalerao, Snehal Raut, Ehsan Nozohouri, Ulrich Bickel and Luca Cucullo
Pharmaceutics 2021, 13(9), 1474; https://doi.org/10.3390/pharmaceutics13091474 - 15 Sep 2021
Cited by 19 | Viewed by 3860
Abstract
Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that [...] Read more.
Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses. The permeability coefficients of [13C12] sucrose and [13C6] mannitol were assessed using a highly sensitive LC-MS/MS procedure. The resulting BBB displayed continuous tight-junction patterns, low permeability to mannitol and sucrose, and quasi-physiological responses to hyperosmolar opening and p-glycoprotein inhibitor treatment, as demonstrated by decreased BBB integrity and increased permeability of rhodamine 123, respectively. Astrocytes and pericytes on the abluminal side of the vascular channel provided the environmental cues necessary to form a tight barrier and extend the model’s long-term viability for time-course studies. In conclusion, our novel multi-culture microfluidic platform showcased the ability to replicate a quasi-physiological brain microvascular, thus enabling the development of a highly predictive and translationally relevant BBB model. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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Review

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23 pages, 5547 KiB  
Review
Microfluidic Manipulation for Biomedical Applications in the Central and Peripheral Nervous Systems
by Zhenghang Li, Zhenmin Jiang, Laijin Lu and Yang Liu
Pharmaceutics 2023, 15(1), 210; https://doi.org/10.3390/pharmaceutics15010210 - 6 Jan 2023
Cited by 4 | Viewed by 2118
Abstract
Physical injuries and neurodegenerative diseases often lead to irreversible damage to the organizational structure of the central nervous system (CNS) and peripheral nervous system (PNS), culminating in physiological malfunctions. Investigating these complex and diverse biological processes at the macro and micro levels will [...] Read more.
Physical injuries and neurodegenerative diseases often lead to irreversible damage to the organizational structure of the central nervous system (CNS) and peripheral nervous system (PNS), culminating in physiological malfunctions. Investigating these complex and diverse biological processes at the macro and micro levels will help to identify the cellular and molecular mechanisms associated with nerve degeneration and regeneration, thereby providing new options for the development of new therapeutic strategies for the functional recovery of the nervous system. Due to their distinct advantages, modern microfluidic platforms have significant potential for high-throughput cell and organoid cultures in vitro, the synthesis of a variety of tissue engineering scaffolds and drug carriers, and observing the delivery of drugs at the desired speed to the desired location in real time. In this review, we first introduce the types of nerve damage and the repair mechanisms of the CNS and PNS; then, we summarize the development of microfluidic platforms and their application in drug carriers. We also describe a variety of damage models, tissue engineering scaffolds, and drug carriers for nerve injury repair based on the application of microfluidic platforms. Finally, we discuss remaining challenges and future perspectives with regard to the promotion of nerve injury repair based on engineered microfluidic platform technology. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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22 pages, 2362 KiB  
Review
Modeling an Optimal 3D Skin-on-Chip within Microfluidic Devices for Pharmacological Studies
by Estibaliz Fernandez-Carro, Maricke Angenent, Tamara Gracia-Cazaña, Yolanda Gilaberte, Clara Alcaine and Jesús Ciriza
Pharmaceutics 2022, 14(7), 1417; https://doi.org/10.3390/pharmaceutics14071417 - 6 Jul 2022
Cited by 10 | Viewed by 6407
Abstract
Preclinical research remains hampered by an inadequate representation of human tissue environments which results in inaccurate predictions of a drug candidate’s effects and target’s suitability. While human 2D and 3D cell cultures and organoids have been extensively improved to mimic the precise structure [...] Read more.
Preclinical research remains hampered by an inadequate representation of human tissue environments which results in inaccurate predictions of a drug candidate’s effects and target’s suitability. While human 2D and 3D cell cultures and organoids have been extensively improved to mimic the precise structure and function of human tissues, major challenges persist since only few of these models adequately represent the complexity of human tissues. The development of skin-on-chip technology has allowed the transition from static 3D cultures to dynamic 3D cultures resembling human physiology. The integration of vasculature, immune system, or the resident microbiome in the next generation of SoC, with continuous detection of changes in metabolism, would potentially overcome the current limitations, providing reliable and robust results and mimicking the complex human skin. This review aims to provide an overview of the biological skin constituents and mechanical requirements that should be incorporated in a human skin-on-chip, permitting pharmacological, toxicological, and cosmetic tests closer to reality. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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22 pages, 3251 KiB  
Review
Recent Development of Drug Delivery Systems through Microfluidics: From Synthesis to Evaluation
by Zhiyuan Ma, Baicheng Li, Jie Peng and Dan Gao
Pharmaceutics 2022, 14(2), 434; https://doi.org/10.3390/pharmaceutics14020434 - 17 Feb 2022
Cited by 28 | Viewed by 5167
Abstract
Conventional drug administration usually faces the problems of degradation and rapid excretion when crossing many biological barriers, leading to only a small amount of drugs arriving at pathological sites. Therapeutic drugs delivered by drug delivery systems to the target sites in a controlled [...] Read more.
Conventional drug administration usually faces the problems of degradation and rapid excretion when crossing many biological barriers, leading to only a small amount of drugs arriving at pathological sites. Therapeutic drugs delivered by drug delivery systems to the target sites in a controlled manner greatly enhance drug efficacy, bioavailability, and pharmacokinetics with minimal side effects. Due to the distinct advantages of microfluidic techniques, microfluidic setups provide a powerful tool for controlled synthesis of drug delivery systems, precisely controlled drug release, and real-time observation of drug delivery to the desired location at the desired rate. In this review, we present an overview of recent advances in the preparation of nano drug delivery systems and carrier-free drug delivery microfluidic systems, as well as the construction of in vitro models on-a-chip for drug efficiency evaluation of drug delivery systems. We firstly introduce the synthesis of nano drug delivery systems, including liposomes, polymers, and inorganic compounds, followed by detailed descriptions of the carrier-free drug delivery system, including micro-reservoir and microneedle drug delivery systems. Finally, we discuss in vitro models developed on microfluidic devices for the evaluation of drug delivery systems, such as the blood–brain barrier model, vascular model, small intestine model, and so on. The opportunities and challenges of the applications of microfluidic platforms in drug delivery systems, as well as their clinical applications, are also discussed. Full article
(This article belongs to the Special Issue Microfluidics in Drug Delivery)
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