Microfluidic Technologies for Drug Delivery

A special issue of Micromachines (ISSN 2072-666X).

Deadline for manuscript submissions: closed (31 October 2016) | Viewed by 34854

Special Issue Editors

Faculty of Engineering and the Environment, University of Southampton, Southampton SO17 1BJ, UK
Interests: microfluidics; drug delivery systems; nanomedicine; bioanalysis; biomicrofluidics
Special Issues, Collections and Topics in MDPI journals
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Medical Sciences Division, University of Oxford, Oxford OX3 7BN, UK
Interests: bio-microfluidics; biomedical microdevices; acoustofluidics; drug delivery; biomedical ultrasound; ultrasound bio-effects; nano- & micro-particles; interventional medicine; physiological models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microfluidic technologies have demonstrated potential for applications in drug delivery. For instance, microfluidic-based devices have been largely employed to produce nano- and micro-scale drug delivery vehicles, providing superior control over the physico-chemical characteristics of the end-product compared to bulk methods. Being able to mimic the physiological microenvironments with a range of biological and physical properties (e.g., organs-on-a-chip), microfluidic systems have also been used as an effective in vitro platform to screen the therapeutic potential of biologically active compounds and stimuli-responsive devices. Furthermore, significant efforts have been devoted to the development of miniaturised systems for localised, controlled delivery of pharmaceutical agents to cells and/or tissues.

In view of a potential clinical translation of this technology however, further efforts should be devoted to: (i) improve scaling-up, high-throughput, operation robustness, and usability by non-specialised personnel; (ii) develop multi-modal delivery vehicles (i.e., for combined imaging, targeting and therapy); (iii) integrate drug formulation, sensing and delivery units on a single technology platform; and (iv) design innovative, cost-effective materials compatible with long-term clinical and industrial applications.

In this Special Issue we aim to showcase research papers, short communications and review articles focusing on the development of microfluidic-based technologies applied to the delivery of therapeutic relevant compounds, encompassing studies dealing with production of drug delivery vehicles, in vitro screening of their therapeutic actions, and localised delivery to target cells and/or tissues. We particularly welcome contributions dealing with ongoing challenges and focusing on translational research.

Dr. Xunli Zhang
Dr. Dario Carugo
Guest Editors

Manuscript Submission Information

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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. Micromachines 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 2600 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
  • synthesis methods
  • in vitro characterisation
  • controlled drug release
  • organs-on-a-chip
  • therapeutic biomicrofluidics
  • microscale bioengineering

Published Papers (6 papers)

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Research

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3682 KiB  
Article
Analysis of the Diffusion Process by pH Indicator in Microfluidic Chips for Liposome Production
by Elisabetta Bottaro, Ali Mosayyebi, Dario Carugo and Claudio Nastruzzi
Micromachines 2017, 8(7), 209; https://doi.org/10.3390/mi8070209 - 01 Jul 2017
Cited by 11 | Viewed by 5762
Abstract
In recent years, the development of nano- and micro-particles has attracted considerable interest from researchers and enterprises, because of the potential utility of such particles as drug delivery vehicles. Amongst the different techniques employed for the production of nanoparticles, microfluidic-based methods have proven [...] Read more.
In recent years, the development of nano- and micro-particles has attracted considerable interest from researchers and enterprises, because of the potential utility of such particles as drug delivery vehicles. Amongst the different techniques employed for the production of nanoparticles, microfluidic-based methods have proven to be the most effective for controlling particle size and dispersity, and for achieving high encapsulation efficiency of bioactive compounds. In this study, we specifically focus on the production of liposomes, spherical vesicles formed by a lipid bilayer encapsulating an aqueous core. The formation of liposomes in microfluidic devices is often governed by diffusive mass transfer of chemical species at the liquid interface between a solvent (i.e., alcohol) and a non-solvent (i.e., water). In this work, we developed a new approach for the analysis of mixing processes within microfluidic devices. The method relies on the use of a pH indicator, and we demonstrate its utility by characterizing the transfer of ethanol and water within two different microfluidic architectures. Our approach represents an effective route to experimentally characterize diffusion and advection processes governing the formation of vesicular/micellar systems in microfluidics, and can also be employed to validate the results of numerical modelling. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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2145 KiB  
Article
Investigation of Drug Cocktail Effects on Cancer Cell-Spheroids Using a Microfluidic Drug-Screening Assay
by Ka I. Au Ieong, Chengpeng Yang, Chin To Wong, Angelie C. Shui, Tom T. Y. Wu, Ting-Hsuan Chen and Raymond H. W. Lam
Micromachines 2017, 8(6), 167; https://doi.org/10.3390/mi8060167 - 24 May 2017
Cited by 13 | Viewed by 6136
Abstract
Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings [...] Read more.
Development of drugs based on potential anti-cancer chemotherapeutic agents has been hindered by its necessary tedious procedures and failure in the clinical trials because of unbearable toxicity and extremely low clinical efficacy. One of the technical challenges is the mismatch between laboratory settings and human body environments for the cancer cells responding upon treatments of the anti-cancer agents. This major limitation urges for applying more reliable platforms for evaluating drugs with a higher throughput and cell aggregates in a more natural configuration. Here, we adopt a microfluidic device integrated with a differential micromixer and multiple microwell-containing channels (50 microwells per channel) for parallel screening of suspending cell spheroids treated by drugs with different combinations. We optimize the culture conditions of the surfactant-coated microwells in order to facilitate the spheroid formation of the breast cancer cell line (MDA-MB-231). We propose a new drug cocktail combined with three known chemotherapeutic agents (paclitaxel, epirubicin, and aspirin) for the drug screening of the cancer cell-spheroids. Our results exhibit the differential responses between planar cell layers in traditional culture wells and cell-spheroids grown in our microfluidic device, in terms of the apoptotic rates under treatments of the drug cocktails with different concentrations. These results reveal a distinct drug resistance between planar cell layers and cell-spheroids. Together, this work offers important guidelines on applying the cell-spheroid microfluidic cultures for development of more efficacious anticancer drugs. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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8183 KiB  
Article
Preparation of Protein Nanoparticles Using NTA End Functionalized Polystyrenes on the Interface of a Multi-Laminated Flow Formed in a Microchannel
by Hyeong Jin Jeon, Chae Yeon Lee, Moon Jeong Kim, Xuan Don Nguyen, Dong Hyeok Park, Hyung Hoon Kim, Jeung Sang Go and Hyun-jong Paik
Micromachines 2017, 8(1), 10; https://doi.org/10.3390/mi8010010 - 03 Jan 2017
Cited by 2 | Viewed by 5252
Abstract
This paper challenges the production of the protein nanoparticles using the conjugation of Ni2+ complexed nitrilotriacetic acid end-functionalized polystyrene (Ni-NTA-PS) and histidine tagged GFP (His-GFP) hybrid. The microfluidic synthesis of the protein nanoparticle with the advantages of a uniform size, a fast [...] Read more.
This paper challenges the production of the protein nanoparticles using the conjugation of Ni2+ complexed nitrilotriacetic acid end-functionalized polystyrene (Ni-NTA-PS) and histidine tagged GFP (His-GFP) hybrid. The microfluidic synthesis of the protein nanoparticle with the advantages of a uniform size, a fast reaction, and a precise control of preparation conditions is examined. The self-assembly occurs on the interfacial surface of the multi-laminated laminar flow stably formed in the microchannel. The clogging of the produced protein nanoparticles on the channel surface is solved by adding a retarding inlet channel. The size and shape of the produced protein nanoparticles are measured by the analysis of transmission electron microscopy (TEM) and scanning electron microscope (SEM) images, and the attachment of the protein is visualized with a green fluorescent image. Future research includes the encapsulation of vaccines and the coating of antigens on the protein surface. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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6354 KiB  
Article
Microfluidic Separation of a Soluble Substance Using Transverse Diffusion in a Layered Flow
by Xuan Don Nguyen, Hyeong Jin Jeon, Hyo Yong Kim, Hyun Jong Paik, June Huh, Hyung Hoon Kim and Jeung Sang Go
Micromachines 2017, 8(1), 9; https://doi.org/10.3390/mi8010009 - 29 Dec 2016
Cited by 2 | Viewed by 5040
Abstract
This paper presents a practical flow-through method to separate anisole and ethyl phenylacetate, respectively, from a polystyrene mixture. The microfluidic separation uses different diffusive dynamics of the substances transverse to the lamination flow formed in a microchannel. The effect of inlet flow rates [...] Read more.
This paper presents a practical flow-through method to separate anisole and ethyl phenylacetate, respectively, from a polystyrene mixture. The microfluidic separation uses different diffusive dynamics of the substances transverse to the lamination flow formed in a microchannel. The effect of inlet flow rates and ambient temperature on separation is examined. Additionally, the possibility of the separation of the light substance from the mixture with different molecular weight is shown numerically and experimentally. The separation efficiency is explained by the facts that the relaxation time depends on the inlet flow rate and that the diffusivity depends on the ambient temperature. This method can be applied to separate monomers from aggregates. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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3624 KiB  
Article
Microfluidic Fabrication of Hydrocortisone Nanocrystals Coated with Polymeric Stabilisers
by David F. Odetade and Goran T. Vladisavljevic
Micromachines 2016, 7(12), 236; https://doi.org/10.3390/mi7120236 - 18 Dec 2016
Cited by 16 | Viewed by 5643
Abstract
Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL [...] Read more.
Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL of HC in a 60:40 (v/v) mixture of ethanol and water and the anti-solvent was milli-Q water. The microfluidic mixers were fabricated with an orifice diameter of the inner capillary ranging from 50 µm to 400 µm and operated at the aqueous to organic phase flow rate ratio ranging from 5 to 25. The size of the nanocrystals decreased with increasing aqueous to organic flow rate ratio. The counter-current flow microfluidic mixers provided smaller nanocrystals than the co-current flow devices under the same conditions and for the same geometry, due to smaller diameter of the organic phase stream in the mixing zone. The Z-average particle size of the drug nanocrystals increased from 210–280 nm to 320–400 nm after coating the nanocrystals with 0.2 wt % aqueous solution of hydroxypropyl methylcellulose (HPMC) in a stirred vial. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses carried out on the dried nanocrystals stabilized with HPMC, polyvinyl pyrrolidone (PVP), and sodium lauryl sulfate (SLS) were investigated and reported. The degree of crystallinity for the processed sample was lowest for the sample stabilised with HPMC and the highest for the raw HC powder. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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Review

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2625 KiB  
Review
Microfabricated Physiological Models for In Vitro Drug Screening Applications
by Giovanni Stefano Ugolini, Daniela Cruz-Moreira, Roberta Visone, Alberto Redaelli and Marco Rasponi
Micromachines 2016, 7(12), 233; https://doi.org/10.3390/mi7120233 - 15 Dec 2016
Cited by 20 | Viewed by 6369
Abstract
Microfluidics and microfabrication have recently been established as promising tools for developing a new generation of in vitro cell culture microdevices. The reduced amounts of reagents employed within cell culture microdevices make them particularly appealing to drug screening processes. In addition, latest advancements [...] Read more.
Microfluidics and microfabrication have recently been established as promising tools for developing a new generation of in vitro cell culture microdevices. The reduced amounts of reagents employed within cell culture microdevices make them particularly appealing to drug screening processes. In addition, latest advancements in recreating physiologically relevant cell culture conditions within microfabricated devices encourage the idea of using such advanced biological models in improving the screening of drug candidates prior to in vivo testing. In this review, we discuss microfluidics-based models employed for chemical/drug screening and the strategies to mimic various physiological conditions: fine control of 3D extra-cellular matrix environment, physical and chemical cues provided to cells and organization of co-cultures. We also envision future directions for achieving multi-organ microfluidic devices. Full article
(This article belongs to the Special Issue Microfluidic Technologies for Drug Delivery)
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