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Microfluidic Technologies for Accelerating the Clinical Translation of Nanoparticles
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Pedro M. Valencia, Omid C. Farokhzad, Rohit Karnik, Robert Langer
In recent years, several microfluidic systems that enable rapid mixing without the need of external actuators, such as stirrers or electric fields, have been developed [19]. The most widely used include flow-focusing mixers [20], droplet mixers [21] and those with micromixing structures embedded inside the channel [22]. Flow focusing squeezes the solvent stream between two anti-solvent streams, resulting in rapid solvent exchange via diffusion (Fig. 3.2b). Droplets and three-dimensional microchannel geometries result in complex folding of fluid flows, which can completely mix two or more streams in milliseconds (Fig. 3.2b). The implementation of these mixing techniques for the formation of organic nanoparticles in continuous flow has resulted in polymeric and lipid nanoparticles with tunable nanoparticle size, narrower size distribution, higher drug loadings and greater batch-to-batch reproducibility relative to those made with conventional bulk techniques [23] (Fig. 3.2c).
Lipid Vesicles for Skin Delivery: Evolution from First Generation
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Tiago Mendes, Maria Manuela Gaspar, Sandra Simöes, Andreia Ascenso
Microfluidic methods, involve fluid flow through channels in the range of 5-500 gm using flow focusing, pulsed jet, thin film hydration and microfluidic droplets techniques. Altering the flow rate, size, polydispersity index and encapsulation efficiency can be modified [40]. The major advantage of this method is dispensing a rigorous volume of liposomal formulation and achieving a precise control of size distribution. Although monodisperse vesicles are obtained in a continuous operating mode, more extensive studies are still needed to solve certain scale-up issues [41].
Targeted Ultrasound Contrast Agents
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Mark A. Borden, Paul A. Dayton
Microfluidic techniques are currently being explored for controlled production of contrast agents. Methods such as flow focusing can result in a contrast agent population with a precise size distribution (Fig. 3A). Flow focusing utilizes micron-sized channels to precisely mix the gas and lipid solution through a micron-sized orifice in a manner which results in nearly identical encapsulated microbubbles. In this way, a population of contrast agents can be tailored to match the desired imaging frequency (47,48). T-junctions (49), jetting (50), and electrohydrodynamic atomization (51) have also been used. Microfluidic technologies will need to show similar robustness and ease of preparation in generating a sufficient microbubble dose. However, the potential gains in control over the size and microbubble surface chemistry could significantly enhance quantification in molecular imaging studies.
Methods for fabricating oxygen releasing biomaterials
Published in Journal of Drug Targeting, 2022
Ahmet Erdem, Reihaneh Haghniaz, Yavuz Nuri Ertas, Siva Koti Sangabathuni, Ali S. Nasr, Wojciech Swieszkowski, Nureddin Ashammakhi
Each of the mentioned methods has its advantages and limitations and the selection of the method should be carefully made (Table 2). The duration of O2 release from fabricated constructs depends on the location of the O2 source in the construct and the properties of the containing polymer. For example, PDMS curing results in very slow O2 release kinetics because PDMS is highly hydrophobic, which can limit the O2 release. Using microfluidic techniques, O2 releasing materials can be embedded deep into the carrier polymers, which can result in slow O2 release. However, microfluidic approaches are much more complex compared to other methods because they require a flow focussing microchip device, and related multiple steps of design and fabrication processes. The time required to produce O2 releasing materials also varies between different approaches where gelation requiring the least time (minutes to an hour) due to the quick solidification of the gelating polymers, and used crosslinking and photoinitiator agents. On the other hand, electrospraying can take days because of the drying process is lengthy. Yield is another parameter that needs to be taken into consideration when producing considerable amounts of O2 releasing materials is required. While gelation produces the highest yield, microfluidic systems and PDMS curing methods suffer from producing samples in low quantities. Quality in terms of homogeneity and the ideal release kinetics, is best obtained with the use of microfluidic approaches.
Microfluidic-based fabrication and characterization of drug-loaded PLGA magnetic microspheres with tunable shell thickness
Published in Drug Delivery, 2021
Chunpeng He, Wenxin Zeng, Yue Su, Ruowei Sun, Yin Xiao, Bolun Zhang, Wenfang Liu, Rongrong Wang, Xun Zhang, Chuanpin Chen
DEB-TACE microspheres should have homogeneous size to make sure the particles would localize and embolize the arterial as the predictable way. Hence, we investigated the size and morphology of the microspheres. A two-phase microfluidics flow-focusing device was designed to generate the microspheres. The microfluidic device designed consists of a flow focusing channel, an outlet and two inlets, in which the flow streams of inner phase were sheared into small droplets by outer phase. The flow rates of outer phase and inner phase, named Qo and Qi, respectively, were investigated to form droplets of different sizes. Inverted fluorescence microscope with bright field was chosen to capture the morphology of the wet microspheres. The result indicated that the particle size decrease with the increase of Qo and the decrease of Qi (Figure 3(A,B)). What is more, the concentration of Fe3O4 NPs and PLGA would make a tremendous difference to the size and size distribution. Figure 3(C) shows that the size increased when increasing the concentration of PLGA, which may because a higher concentration leaded to a higher viscosity, and the latter is an important factor for microsphere preparation. However, the high-viscosity fluid would increase the risk of micro-channel blocking.
Nano-carriers for drug routeing – towards a new era
Published in Journal of Drug Targeting, 2019
Harivardhan Reddy Lakkireddy, Didier V. Bazile
When nano-carriers are manufactured by precipitation (sometimes referred to as ‘bottom up’ method), the reproducibility of the sophisticated structures presented earlier is dependent upon the mixing time of the solvent and non-solvent solutions as compared to the time of nano-assembly. While conditions where Tmixing<Taggregation have been difficult to meet using ‘in batch’ manufacturing in reactors, the advent of microfluidics, and in particular hydrodynamic flow focussing, has given access to process control at the microscopic scale [133]. Therefore, the predictability of the bottom up assembly of complex systems using microfluidics is prone to reconcile the challenges of nano-carriers manufacturing with the constraints of the Quality by Design approach advocated by the industrial partners [134]. Even if the feasibility of the scale up based on the parallelisation of flow focussing systems has still to tested in the Good Manufacturing Practices (GMP) industrial context, the data obtained with up to 100 outlets are encouraging [135].