Special Issue "Microfluidics as a Tool for Drug Delivery"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (5 August 2021).

Special Issue Editors

Prof. Dr. Sudip K. Das
E-Mail Website
Guest Editor
College of Pharmacy & Health Sciences, Butler University, Indianapolis, IN 46208, USA
Interests: nanomedicine; biomaterials & bioengineering; targeted delivery of anticancer drugs; non-viral gene delivery; 3D cell culture; microfluidics

Special Issue Information

Dear Colleagues,

Microfluidics is a technology that allows precise control and manipulation of very small fluid flows, which translates to small amounts of reagents used more simply, and faster. The technologies are key in the development of novel applications in different fields, including drug discovery, drug delivery, in vitro diagnostics, chemical analysis and high-throughput screening. In the field of drug delivery, for example, micro and nanoparticle (e.g., polymeric, lipid) drug delivery systems provide superior control over the physicochemical characteristics of the final product. This Special Issue will address the new developments in the area of Microfluidics, including the development of efficient drug carrier particles, as rapid techniques for direct drug screening (e.g., plasma drug level monitoring), for dilution or mixing of pharmaceutical chemical reagents, and the formulation of microfluidic systems with self-contained reservoirs that provide continuous drug release over an extended period. Original research papers and review articles are welcomed.

Dr. Dimitrios A. Lamprou
Prof. Dr. Sudip K. Das
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 papers will be 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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 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

  • chip manufacturing
  • controlled drug delivery
  • drug delivery systems
  • drug screening
  • formulation
  • microfluidics
  • microparticles
  • nanoparticles
  • pharmaceutics
  • therapeutic biomicrofluidics

Published Papers (6 papers)

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Research

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Article
Optimization of Production Parameters for Andrographolide-Loaded Nanoemulsion Preparation by Microfluidization and Evaluations of Its Bioactivities in Skin Cancer Cells and UVB Radiation-Exposed Skin
Pharmaceutics 2021, 13(8), 1290; https://doi.org/10.3390/pharmaceutics13081290 - 18 Aug 2021
Viewed by 660
Abstract
Andrographolide (AG) is an active compound isolated from Andrographis paniculata (Family Acanthaceae). Although it possesses beneficial bioactivities to the skin, there is insufficient information of its applications for treatment of skin disorders due to low water solubility leading to complications in product development. [...] Read more.
Andrographolide (AG) is an active compound isolated from Andrographis paniculata (Family Acanthaceae). Although it possesses beneficial bioactivities to the skin, there is insufficient information of its applications for treatment of skin disorders due to low water solubility leading to complications in product development. To overcome the problem, an AG-loaded nanoemulsion (AG-NE) was formulated and prepared using a microfluidization technique. This study aimed to investigate the effect of pressure and the number of homogenization cycles (factors) on droplet size, polydispersity index and zeta potential of AG-NE (responses) and to determine the effect of AG-NE on skin cancer cells and UVB irradiation-induced skin disorders in rats. Relationships between factors versus responses obtained from the face-centered central composite design were described by quadratic models. The optimum value of parameters for the production of optimized AG-NE (Op-AG-NE) were 20,000 psi of pressure and 5 homogenization cycles. Op-AG-NE showed promising cytotoxicity effects on the human malignant melanoma- (A375 cells) and non-melanoma cells (A-431 cells) via apoptosis induction with a high selectivity index and also inhibited intracellular tyrosinase activity in the A375 cells. Op-AG-NE could reduce melanin index and healed UVB irradiation exposed skin. Op-AG-NE thus had potential for treatment of skin cancers and skin disorders from exposure to UVB radiation. Full article
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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Article
3D Printed Microfluidic Devices for Drug Release Assays
Pharmaceutics 2021, 13(1), 13; https://doi.org/10.3390/pharmaceutics13010013 - 23 Dec 2020
Cited by 3 | Viewed by 1176
Abstract
Microfluidics research for various applications, including drug delivery, cell-based assays and biomedical research has grown exponentially. Despite this technology’s enormous potential, drawbacks include the need for multistep fabrication, typically with lithography. We present a one-step fabrication process of a microfluidic chip for drug [...] Read more.
Microfluidics research for various applications, including drug delivery, cell-based assays and biomedical research has grown exponentially. Despite this technology’s enormous potential, drawbacks include the need for multistep fabrication, typically with lithography. We present a one-step fabrication process of a microfluidic chip for drug dissolution assays based on a 3D printing technology. Doxorubicin porous and non-porous microspheres, with a mean diameter of 250µm, were fabricated using a conventional “batch” or microfluidic method, based on an optimized solid-in-oil-in-water protocol. Microspheres fabricated with microfluidics system exhibited higher encapsulation efficiency and drug content as compared with batch formulations. We determined drug release profiles of microspheres in varying pH conditions using two distinct dissolution devices that differed in their mechanical barrier structures. The release profile of the “V” shape barrier was similar to that of the dialysis sac test and differed from the “basket” barrier design. Importantly, a cytotoxicity test confirmed biocompatibility of the printed resin. Finally, the chip exhibited high durability and stability, enabling multiple recycling sessions. We show how the combination of microfluidics and 3D printing can reduce costs and time, providing an efficient platform for particle production while offering a feasible cost-effective alternative to clean-room facility polydimethylsiloxane-based chip microfabrication. Full article
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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Article
Wearable Fixation Device for a Magnetically Controllable Therapeutic Agent Carrier: Application to Cartilage Repair
Pharmaceutics 2020, 12(6), 593; https://doi.org/10.3390/pharmaceutics12060593 - 26 Jun 2020
Viewed by 863
Abstract
Recently, significant research efforts have been devoted toward the development of magnetically controllable drug delivery systems, however, drug fixation after targeting remains a challenge hindering long-term therapeutic efficacy. To overcome this issue, we present a wearable therapeutic fixation device for fixing magnetically controllable [...] Read more.
Recently, significant research efforts have been devoted toward the development of magnetically controllable drug delivery systems, however, drug fixation after targeting remains a challenge hindering long-term therapeutic efficacy. To overcome this issue, we present a wearable therapeutic fixation device for fixing magnetically controllable therapeutic agent carriers (MCTACs) at defect sites and its application to cartilage repair using stem cell therapeutics. The developed device comprises an array of permanent magnets based on the Halbach array principle and a wearable band capable of wrapping the target body. The design of the permanent magnet array, in terms of the number of magnets and array configuration, was determined through univariate search optimization and 3D simulation. The device was fabricated for a given rat model and yielded a strong magnetic flux density (exceeding 40 mT) in the region of interest that was capable of fixing the MCTAC at the desired defect site. Through in-vitro and in-vivo experiments, we successfully demonstrated that MCTACs, both a stem cell spheroid and a micro-scaffold for cartilage repair, could be immobilized at defect sites. This research is expected to advance precise drug delivery technology based on MCTACs, enabling subject-specific routine life therapeutics. Further studies involving the proposed wearable fixation device will be conducted considering prognostics under actual clinical settings. Full article
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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Article
Multi-Compartment 3D-Cultured Organ-on-a-Chip: Towards a Biomimetic Lymph Node for Drug Development
Pharmaceutics 2020, 12(5), 464; https://doi.org/10.3390/pharmaceutics12050464 - 19 May 2020
Cited by 13 | Viewed by 3386
Abstract
The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but [...] Read more.
The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but significant building blocks that enable such immune-drug studies. We developed a novel microfluidic platform replicating the Lymph Node (LN) microenvironment called LN-on-a-chip, starting from design all the way to microfabrication, characterization and validation in terms of architectural features, fluidics, cytocompatibility, and usability. To prove the biomimetics of this microenvironment, we inserted different immune cell types in a microfluidic device, which showed an in-vivo-like spatial distribution. We demonstrated that the developed LN-on-a-chip incorporates key features of the native human LN, namely, (i) similarity in extracellular matrix composition, morphology, porosity, stiffness, and permeability, (ii) compartmentalization of immune cells within distinct structural domains, (iii) replication of the lymphatic fluid flow pattern, (iv) viability of encapsulated cells in collagen over the typical timeframe of immunotoxicity experiments, and (v) interaction among different cell types across chamber boundaries. Further studies with this platform may assess the immune cell function as a step forward to disclose the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments. Full article
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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Article
On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation
Pharmaceutics 2020, 12(3), 260; https://doi.org/10.3390/pharmaceutics12030260 - 13 Mar 2020
Cited by 8 | Viewed by 1043
Abstract
In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, [...] Read more.
In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, using a staggered herringbone micromixer, allowed to produce HA/CS NPs with tailored-made size and suitable for both parenteral (117.50 ± 4.51 nm) and loco-regional (349.15 ± 38.09 nm) administration, mainly composed by HA (more than 85% wt) with high negative surface charge (< −20 mV). HA/CS NPs were successfully loaded with a challenging water-insoluble molecule, Everolimus (EVE), an FDA- and EMA-approved anticancer drug able to lead to cell cycle arrest, reduced angiogenesis and promotion of apoptosis. HA/CS NPs resulted to be massively internalized in CD44+ human mesenchymal stem cells via CD44 receptor-mediated endocytosis. HA/CS NPs selectiveness towards CD44 was highlighted by blocking CD44 receptor by anti-CD44 primary antibody and by comparison to CS-based NPs cellular uptake. Eventually, high effectiveness in inhibiting cell proliferation was demonstrated on-chip synthetized EVE loaded HA/CS NPs by tracking in vitro DNA synthesis. Full article
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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Review

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Review
Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies
Pharmaceutics 2020, 12(6), 542; https://doi.org/10.3390/pharmaceutics12060542 - 11 Jun 2020
Cited by 8 | Viewed by 1775
Abstract
Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these [...] Read more.
Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation. Full article
(This article belongs to the Special Issue Microfluidics as a Tool for Drug Delivery)
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