Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow‐Focusing Device for Controlled Drug Delivery

Abstract

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several FDA-approved therapies. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug delivery properties of those particles. Particles were engineered with defined sizes, ranging from 10 μm to 50 μm. These particles were nearly monodisperse (polydispersity index = 3.9 %). We incorporated a model amphiphilic drug (bupivacaine) within the biodegradable matrix of the particles. Kinetic analysis showed that the release of drug from these monodisperse particles was slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibited a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release was attributed to the uniform distribution of drug inside the particles generated using the microfluidic methods. These results demonstrated the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs.

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

“…7,41 In addition, although the smaller particles tend to cause undesirable burst releases, 42 larger particles can pose problems in microcirculation due to their inability to travel through small blood capillaries. The capability to segregate polydisperse particles into different size ranges is highly useful for in vivo drug delivery studies and organ-specific applications.…”

“…2 In microparticle fabrication, conventional 'bottom-up' self-assembly emulsification techniques yield a broad particle size distribution, which can affect the drug release kinetics and biotransport in blood. 3,4 Although well-controlled and monodisperse particles can be produced by 'top-down' approaches using specific lithographic techniques 5,6 and microfluidics, 7,8 microfabricated particles are prone to damage during mechanical harvesting, a problem further aggravated at the smaller/nanoscale level. Similarly, microfluidic synthesis of drug-loaded polymeric particles requires compatible drug/surfactant chemistry with additional steps to remove solvent prior use.…”

Observation and Manipulation of a Capillary Jet in a Centrifuge-Based Droplet Shooting Device

“…Manipulation and gelation of polymer liquid flow in microfluidic devices is a powerful approach to produce micro-particles for various applications such as multiplexing assay [1,2], platforms for biological analysis [3], photonic devices [4], drug carriers [5], and scaffolds for tissue engineering [6]. Microfluidic devices, such as T-junction [7] and flow-focusing [8] often use a system of co-flowing immiscible liquid for stable production of monodisperse polymeric droplets/particles.…”

Microfluidic formulation of pectin microbeads for encapsulation and controlled release of nanoparticles

“…10 Extensions of these techniques are used to encapsulate biomaterials, 11 prepare microbubble contrast agents for ultrasound radiography, 12 carriers of active substances for targeted drug delivery, 13 and for control of the temporal profile of their release. 14 Microfluidics offers extensive and unique control over the distribution of volumes of particles and over the process of their gelation. This prompts further development of microfluidic techniques for formulation of biocompatible particles of biopolymers and hydrogels for the applications in pharmacology and medicine.…”

“…The separation of cells from the host tissue enhances the efficacy and viability of transplanted cells. 18 Likewise, they are used to encapsulate microorganisms ͑e.g., yeast 19 for the fermentation processes͒ or active substances like drugs, 14,20 enzymes, 11 or even blood proteins. 21 As opposed to traditional, physicochemical methods of encapsulation, also here microfluidics comes in with a unique advantage of the possibility to encapsulate virtually any material in any matrix via the hydrodynamic control of the process of formation of particles.…”