Integrated system to produce nano/microparticles for drug delivery using LTCC microfluidics devices (original) (raw)
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Additional Conferences (Device Packaging, HiTEC, HiTEN, and CICMT), 2015
Nanotechnology develops methods and processes for Drug Delivery Systems (DDS) based on the fabrication of polymeric nano/microparticles with encapsulated drug that can be applied for maximize therapeutic activity and minimizes undesirable effects. However, these processes entail several conditions to operate efficiently. They present high sensibility to changes in temperature, flow rate, pressure, and chemical solution composition. An optimal configuration of these parameters is required to guarantee stable particle production. For these reasons, integration of technological devices like sensors, actuators, microfluidic devices and control systems is essential to increase particle production performance. The proposal of this work is to develop an integrated monitored and controlled system using LTCC (Low Temperature Co-Fired Ceramic) microreactors to generate polymeric nano/microparticles for encapsulation of hydrocortisone drug with PCL and Pluronic polymers. The microfluidic integ...
Continuous Regime Microfluidic System for Nanocapsules Generation
2017
This research aims to develop a microfluidic system for chemical process miniaturization for nanocapsules generation. The emulsification, diffusion and solvent extraction/evaporation process was selected as target for miniaturization. LTCC was the selected substrate. Experiments showed the viability of controlling nanocapsules sizing by means of total flow rate through devices. Generated nanocapsules size varied between 790,5 nm ± 36,9 nm and 209,7 nm ± 3,5 nm with a polydispersity index (pdi) between 0,313 ± 0,016 and 0,09 ± 0,017 when flow rate varied between 90 mL/min and 293 mL/min. Other experiments were carried out up to 323 mL/min obtaining nanocapsules sizes down to 193 nm and pdi of 0,109. The flow rate working region is an order of magnitude higher than reported devices which bases its functioning in micromixers. Research results show the developed system potentiality in reducing the existing gap between laboratory and chemical process industry for microfluidic devices. Ke...
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Active pharmaceutical ingredients (API) with suboptimal pharmacokinetic properties may require formulation into nanoparticles. In addition to the quality of the excipients, production parameters are crucial for producing nanoparticles which reliably deliver APIs to their target. Microfluidic platforms promise increased control over the formulation process due to the decreased degrees of freedom at the micro- and nanoscale. Publications about these platforms usually provide only limited information about the soft- and hardware required to integrate the microfluidic chip seamlessly into an experimental set-up. We describe a modular, low-budget prototype for microfluidic mixing in detail. The prototype consists of four modules. The control module is a raspberry pi executing customizable python scripts to control the syringe pumps and the fraction collector. The feeding module consists of up to three commercially available, programable syringe pumps. The formulation module can be any ma...
Microfluidics for pharmaceutical nanoparticle fabrication: The truth and the myth
International Journal of Pharmaceutics, 2020
Using micro-sized channels to manipulate fluids is the essence of microfluidics which has wide applications from analytical chemistry to material science and cell biology research. Recently, using microfluidic-based devices for pharmaceutical research, in particular for the fabrication of micro-and nano-particles, has emerged as a new area of interest. The particles that can be prepared by microfluidic devices can range from micron size droplet-based emulsions to nano-sized drug loaded polymeric particles. Microfluidic technology poses unique advantages in terms of the high precision of the mixing regimes and control of fluids involved in formulation preparation. As a result of this, monodispersity of the particles prepared by microfluidics is often recognised as being a particularly advantageous feature in comparison to those prepared by conventional large-scale mixing methods. However, there is a range of practical drawbacks and challenges of using microfluidics as a direct micron-and nano-particle manufacturing method. Technological advances are still required before this type of processing can be translated for application by the pharmaceutical industry. This review focuses specifically on the application of microfluidics for pharmaceutical solid nanoparticle preparation and discusses the theoretical foundation of using the nanoprecipitation principle to generate particles and how this is translated into microfluidic design and operation.
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Journal of Controlled Release, 2014
The development of new and improved particle-based drug delivery is underpinned by an enhanced ability to engineer particles with high fidelity and integrity, as well as increased knowledge of their biological performance. Microfluidics can facilitate these processes through the engineering of spatiotemporally highly controlled environments using designed microstructures in combination with physical phenomena present at the microscale. In this review, we discuss microfluidics in the context of addressing key challenges in particle-based drug delivery. We provide an overview of how microfluidic devices can: (i) be employed to engineer particles, by providing highly controlled interfaces, and (ii) be used to establish dynamic in vitro models that mimic in vivo environments for studying the biological behavior of engineered particles. Finally, we discuss how the flexible and modular nature of microfluidic devices provides opportunities to create increasingly realistic models of the in vivo milieu (including multi-cell, multi-tissue and even multi-organ devices), and how ongoing development toward commercialization of microfluidic tools are opening up new opportunities for the engineering and evaluation of drug delivery particles.
Journal of Controlled Release, 2010
The present paper describes the production, using a microfluidic approach, of microparticles (constituted of cellulose acetate) and O/ W emulsions (constituted of PEG-6 corn oil droplets). The general production strategy is based on the formation of water-in-oil multiphase flow by a focusing mechanism (X-junction chip). The innovative aspect of the work is represented by the fabrication procedure for the microfluidic chip production. The chips were designed and fabricated by a low cost approach using a shrinkable biocompatible polymer.
Engineering Polymer Microparticles by Droplet Microfluidics
Journal of Flow Chemistry, 2013
Capillary-based flow-focusing and co-flow microsystems were developed to produce polymer microparticles of adjustable sizes in the range of 50 to 600 µm with a narrow size distribution (CV<5%), different shapes (spheres, rods) and morphologies (core-shell, janus, capsules). Influence of operating conditions (flow rate of the different fluid, microsystem characteristic dimensions and design) as well as material parameters (viscosity of the different fluids, surface tension) was investigated. Empirical relationships were thus derived from experimental data to predict microparticle overall size, shell thickness or rods length. Besides morphology, microparticles with various compositions were synthesized and their potential applications highlighted: drug loaded microparticles for new drug delivery strategies, composed inorganic-organic multiscale microparticles for sensorics and liquid crystalline elastomer microparticles showing an anisotropic reversible shape change upon temperature for thermal actuators or artificial muscles.
2009
Polymeric microparticles with hexagonal surface patterns comprising of colloids or dimples were fabricated using photocurable emulsion droplets. Colloidal silica particles within the interior of the photocurable emulsion droplets formed two-dimensional (2D) crystals at the droplet surface by anchoring on the emulsion interface, and the resulting composite structures were captured by rapid photopolymerization. A microfluidic device composed of two coaxial glass capillaries was used to generate monodisperse microparticles, with the evolution time determining the area of the anchored colloidal silica particles on the microparticle that was exposed to the continuous phase. The exposed region of silica particles could be modified by the introduction of desired functional groups such as dye molecules through simple chemical reaction with a silane coupling agent. This ability to modify the surface should prove useful in many applications such as chemical or biomolecular screening and colloidal barcoding systems.
Scientific Reports, 2022
Droplet microfluidic has been established to synthesize and functionalize micro/nanoparticles for drug delivery and screening, biosensing, cell/tissue engineering, lab-on-a-chip, and organ-on-achip have attracted much attention in chemical and biomedical engineering. Chitosan (CS) has been suggested for different biomedical applications due to its unique characteristics, such as antibacterial bioactivities, immune-enhancing influences, and anticancer bioactivities. The simulation results exhibited an alternative for attaining visions in this complex method. In this regard, the role of the flow rate ratio on the CS droplet features, including the generation rate and droplet size, were thoroughly described. Based on the results, an appropriate protocol was advanced for controlling the CS droplet properties for comparing their properties, such as the rate and size of the CS droplets in the microchip. Also, a level set (LS) laminar two-phase flow system was utilized to study the CS dropletbreaking process in the Flow Focused-based microchip. The outcomes demonstrated that different sizes and geometries of CS droplets could be established via varying the several parameters that validated addressing the different challenges for several purposes like drug delivery (the droplets with smaller sizes), tissue engineering, and cell encapsulation (the droplets with larger sizes), lab-on-achip, organ-on-a-chip, biosensing and bioimaging (the droplets with different sizes). An experimental study was added to confirm the simulation results. A drug delivery application was established to verify the claim. Monodisperse micro/nanoparticles with the same morphology and size have attracted much attention in labon-a-chip 1,2 , aptasensors 3,4 , biosensors 5-7 , drug delivery 8-10 , tissue engineering 10 , catalysis 11 , and electro/optic devices 12. Many attempts have been established to generate uniform micro/nano-particles with on-demand and required morphologies, shapes, and sizes by conventional approaches, including dispersion polymerization 13 , emulsion polymerization 14 , precipitation polymerization 15 , layer-by-layer assemblies 16 , and shirasu porous glass (SPG) membrane emulsification 17. However, the typical emulsion droplet approaches are irrepressible. The generated droplets (particularly the non-spherical) are divergent in shape and size 18. Due to the interfacial tensions between the two phases, the conventional techniques to produce droplets shrink into spheres, making it hard to provide suitable shaped micro/nanoparticles (with high quality) 9,19. Furthermore, typical techniques are costly, inflexible, time-consuming, and complex. Thus, superior approaches are required to generate monodisperse micro/nano-particles with on-demand morphology, shape, and size. Microfluidics and nanofluidics are the sciences and technologies of the systems with integrated channels in micro-scaled and nano-scaled sizes (10 to 100 µm and nm), in which minimal amounts of fluids (generally 1 L to 10 −9 L) may flow in desired fabrication manipulated and controlled systematically 19. Droplet microfluidics has attracted much attention in material fabrication and biomedical devices 20. Droplet microfluidics, including passive hydrodynamic pressure 21 and active external actuation 22 techniques, are promising for generating monodisperse micro/nanoparticles. The critical difference is the external forces required for the active method, including