Sustained release of hydrophobic drugs by the microfluidic assembly of multistage microgel/poly (lactic-co-glycolic acid) nanoparticle composites

Hsu, Myat Noe; Luo, Rui; Zeming, Kerwin Kwek; Por, Yong Chen; Zhang, Yong; Chen, Chia-Hung

doi:10.1063/1.4916230

Cited by 38 publications

(21 citation statements)

References 35 publications

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“…Microscale PEGDA hydrogel particles, or “microgels” are of emerging importance to the sensing 22 , drug 23 and tissue engineering 24 communities due to intraparticle diffusion, facile antibody 25 or oligonucleotide conjugation 26 , and potential for in vivo applications 17,27,28 . PEG microgels have been successfully fabricated via stop-flow lithography, a single-phase microfluidic step-wise photopolymerization technique.…”

Section: Introductionmentioning

confidence: 99%

Monodisperse polyethylene glycol diacrylate hydrogel microsphere formation by oxygen-controlled photopolymerization in a microfluidic device

2016

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PEG-based hydrogels have become widely used as drug delivery and tissue scaffolding materials. Common among PEG hydrogel-forming polymers are photopolymerizable acrylates such as polyethylene glycol diacrylate (PEGDA). Microfluidics and microfabrication technologies have recently enabled the miniaturization of PEGDA structures, thus enabling many possible applications for nano- and micro- structured hydrogels. The presence of oxygen, however, dramatically inhibits the photopolymerization of PEGDA, which in turn frustrates hydrogel formation in environments of persistently high oxygen concentration. Using PEGDA that has been emulsified in fluorocarbon oil via microfluidic flow focusing within polydimethylsiloxane (PDMS) devices, we show that polymerization is completely inhibited below critical droplet diameters. By developing an integrated model incorporating reaction kinetics and oxygen diffusion, we demonstrate that the critical droplet diameter is largely determined by the oxygen transport rate, which is dictated by the oxygen saturation concentration of the continuous oil phase. To overcome this fundamental limitation, we present a nitrogen micro-jacketed microfluidic device to reduce oxygen within the droplet, enabling the continuous on-chip photopolymerization of microscale PEGDA particles.

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Section: Introductionmentioning

confidence: 99%

Monodisperse polyethylene glycol diacrylate hydrogel microsphere formation by oxygen-controlled photopolymerization in a microfluidic device

2016

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“…The assembly of sustained release composites of hydrophobic drugs in nanoparticles using microfluidic devices was recently reported. 19 Fluorescence was used to detect the encapsulation of the hydrophobic drugs in the particles that exhibited improved release. UV imaging approaches have also been applied to study the release of drugs from a range of delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Attenuated total reflection-Fourier transform infrared spectroscopic imaging of pharmaceuticals in microfluidic devices

2016

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The poor aqueous solubility of many active pharmaceutical ingredients presents challenges for effective drug delivery. In this study, the combination of attenuated total reflection (ATR)-FTIR spectroscopic imaging with specifically designed polydimethylsiloxane microfluidic devices to study drug release from pharmaceutical formulations has been developed. First, the high-throughput analysis of the dissolution of micro-formulations studied under flowing conditions has been introduced using a model formulation of ibuprofen and polyethylene glycol. The behaviour and release of the drug was monitored in situ under different pH conditions. In contrast to the neutral solution, where both the drug and excipient dissolved at a similar rate, structural change from the molecularly dispersed to a crystalline form of ibuprofen was characterised in the obtained spectroscopic images and the corresponding ATR-FTIR spectra for the experiments carried out in the acidic medium. Further investigations into the behaviour of the drug after its release from formulations (i.e., dissolved drug) were also undertaken. Different solutions of sodium ibuprofen dissolved in a neutral medium were studied upon contact with acidic conditions. The phase transition from a dissolved species of sodium ibuprofen to the formation of solid crystalline ibuprofen was revealed in the microfluidic channels. This innovative approach could offer a promising platform for high-throughput analysis of a range of micro-formulations, which are of current interest due to the advent of 3D printed pharmaceutical and microparticulate delivery systems. Furthermore, the ability to study dissolved drug in solution under flowing conditions can be useful for the studies of the diffusion of drugs into tissues or live cells.

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“…However, NDDS have little relevance for bioactive species that are very soluble in body fluids and diffuse out very rapidly. They are of more interest for hydrophobic species which usually have longer retention times [73,74].…”

Section: Drug Releasementioning

confidence: 99%

Engineered nanomaterials and human health: Part 2. Applications and nanotoxicology (IUPAC Technical Report)

Gubala

Johnston

Krug

et al. 2018

Pure and Applied Chemistry

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Research on engineered nanomaterials (ENM) has progressed rapidly from the very early stages of studying their unique, size-dependent physicochemical properties and commercial exploration to the development of products that influence our everyday lives. We have previously reviewed various methods for synthesis, surface functionalization, and analytical characterization of ENM in a publication titled ‘Engineered Nanomaterials: Preparation, Functionalization and Characterization’. In this second, inter-linked document, we first provide an overview of important applications of ENM in products relevant to human healthcare and consumer goods, such as food, textiles, and cosmetics. We then highlight the challenges for the design and development of new ENM for bio-applications, particularly in the rapidly developing nanomedicine sector. The second part of this document is dedicated to nanotoxicology studies of ENM in consumer products. We describe the various biological targets where toxicity may occur, summarize the four nanotoxicology principles, and discuss the need for careful consideration of the biodistribution, degradation, and elimination routes of nanosized materials before they can be safely used. Finally, we review expert opinions on the risk, regulation, and ethical aspects of using engineered nanomaterials in applications that may have direct or indirect impact on human health or our environment.

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Sustained release of hydrophobic drugs by the microfluidic assembly of multistage microgel/poly (lactic-co-glycolic acid) nanoparticle composites

Cited by 38 publications

References 35 publications

Monodisperse polyethylene glycol diacrylate hydrogel microsphere formation by oxygen-controlled photopolymerization in a microfluidic device

Monodisperse polyethylene glycol diacrylate hydrogel microsphere formation by oxygen-controlled photopolymerization in a microfluidic device

Attenuated total reflection-Fourier transform infrared spectroscopic imaging of pharmaceuticals in microfluidic devices

Engineered nanomaterials and human health: Part 2. Applications and nanotoxicology (IUPAC Technical Report)

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