Microfluidics for Advanced Drug Delivery Systems

Abstract

Considerable efforts have been devoted towards developing effective drug delivery methods. Microfluidic systems, with their capability for precise handling and transport of small liquid quantities, have emerged as a promising platform for designing advanced drug delivery systems. Thus, microfluidic systems have been increasingly used for fabrication of drug carriers or direct drug delivery to a targeted tissue. In this review, the recent advances in these areas are critically reviewed and the shortcomings and opportunities are discussed. In addition, we highlight the efforts towards developing smart drug delivery platforms with integrated sensing and drug delivery components.

Figure 1.

Microfluidic platforms for production of drug and gene carriers. a) Schematics of niosome self-assembly via HFF in a diffusion-based microfluidic mixer (10 nm < D_p <100 nm); reprint with permission from[20]. b) Fabrication of lipid nanoparticle (LNP) small interfering RNA (siRNA) formulation strategy employing the staggered herringbone micromixer (20 nm < Dp < 100 nm); reprint with permission from[29]. c) A multi-inlet microfluidic HFF system to generate lipopolyplex containing Bcl-2 antisense deoxyoligonucleotide (100 nm < D_p < 300 nm); reprint with permission from[30]. d) Droplet-based microfluidic platform for open-celled porous poly(N-isopropylacrylamide) (PNIPAM) microgel production (150 μm < Dp < 450 μm), e) SEM micrographs of fabricated PNIPAM microgels with open-celled porous structure; reprint with permission from [32] f) Fabrication of microgel capsules that consist of two miscible yet distinct layers using double emulsion template in the droplet-based microfluidic device (20 μm < D_p < 100 μm); reprint with permission from [6]. g) Programmable microfluidic array for producing a combinatorial library of DNA encapsulated supramolecular particles; reprint with permission from (40 nm < D_p < 200 μm) [44].

Figure 2.

Microfluidic systems for fabrication of non-spherical particles and carriers. a) nonspherical particles formed by coalescence of spherical particles; reprint with permission from [48]. b) tropoid-like particles fabricated using microfluidic emulsion followed by controlled solvent evaporation; reprint with permission from [49]. c) Stop flow lithography for fabrication of planar particles. (i) schematic of the system, (ii, iii) typical fabricated planar particles using flow lithography; reprint with permission from [52,53]. d) Two-photon continuous flow lithography for fabrication of 3D particles. (i) schematic of the process, (ii) and (iii) bright field and florescent images of a fabricated helical structure; reprint with permission from [54].

Figure 3.

Microfluidic systems for direct drug delivery. a) Implantation of a microfluidic drug delivery platform for ocular applications, where the drug reservoir was sutured to the sclera and placed underneath the conjunctiva. b) Components of the employed drug delivery platform; reprint with permission from [57]. c) Drug delivery platform that the application of electrical field between the top and bottom electrodes introduced bubbles in the chamber which leads to drug release; reprint with permission from [58]. d) A schematic and an image of a wireless microfluidic system for controlling the flight of Manduca sexta; reprint with permission from [59]. e) A microfluidic drug delivery in which heaters generated bubbles to break the membrane and release the drug, f) Side view of the device illustrating methylene blue release; reprint with permission from[60]. g) Principle of operation of a magnetically actuated drug delivery system; reprint with permission from [61]. h) Various types of microneedle arrays; reprint with permission from [66]. j) SEM images of hollow metal (i,iii) and glass (ii) microneedles. (iv) an array of 500 μm long tapered metal microneedles next to a 26-gauge needle; reprint with permission from [62].

Figure 4.

Smart microfluidic systems for drug delivery. a) schematic diagram of a miniature biosensor immobilized on the backside of the gold lid of a microfabricated vial, which is either closed or open after electroactuation by the application of 800 mV versus Ag/AgCl; reprint with permission from [68]. b) Controlled transdermal drug delivery from hydrocolloid and m-silica nanoparticles (NPs) by thermal actuation. Wearable electronic patch composed of the data storage modules, diagnostic tools and therapeutic actuating elements; reprint with permission from [70].