-
Biomedical Microdevices Aug 2018In recent years, there has been growing interest in optically-encoded or tagged functionalized microbeads as a solid support platform to capture proteins or nucleotides... (Review)
Review
In recent years, there has been growing interest in optically-encoded or tagged functionalized microbeads as a solid support platform to capture proteins or nucleotides which may serve as biomarkers of various diseases. Multiplexing technologies (suspension array or planar array) based on optically encoded microspheres have made possible the observation of relatively minor changes in biomarkers related to specific diseases. The ability to identify these changes at an early stage may allow the diagnosis of serious diseases (e.g. cancer) at a time-point when curative treatment may still be possible. As the overall accuracy of current diagnostic methods for some diseases is often disappointing, multiplexed assays based on optically encoded microbeads could play an important role to detect biomarkers of diseases in a non-invasive and accurate manner. However, detection systems based on functionalized encoded microbeads are still an emerging technology, and more research needs to be done in the future. This review paper is a preliminary attempt to summarize the state-of-the-art concerning diagnostic microbeads; including microsphere composition, synthesis, encoding technology, detection systems, and applications.
Topics: Cell Line, Tumor; Computer Simulation; Flow Cytometry; Fluorescent Dyes; Humans; Microarray Analysis; Microspheres; Nanoparticles; Neoplasms; Optical Phenomena; Polymerization; Proteins; Surface Properties
PubMed: 30088103
DOI: 10.1007/s10544-018-0314-4 -
Drug Delivery Dec 2021Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent... (Review)
Review
Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and mechanical strength. PLAG are specifically used as microspheres for the sustained/controlled and targeted delivery of hydrophilic or hydrophobic drugs, as well as biological therapeutic macromolecules, including peptide and protein drugs. PLGAs with different molecular weights, lactic acid (LA)/glycolic acid (GA) ratios, and end groups exhibit unique release characteristics, which is beneficial for obtaining diverse therapeutic effects. This review aims to analyze the composition of PLGA microspheres, and understand the manufacturing process involved in their production, from a quality by design perspective. Additionally, the key factors affecting PLGA microsphere development are explored as well as the principles involved in the synthesis and degradation of PLGA and its interaction with active drugs. Further, the effects elicited by microcosmic conditions on PLGA macroscopic properties, are analyzed. These conditions include variations in the organic phase (organic solvent, PLGA, and drug concentration), continuous phase (emulsifying ability), emulsifying stage (organic phase and continuous phase interaction, homogenization parameters), and solidification process (relationship between solvent volatilization rate and curing conditions). The challenges in achieving consistency between batches during manufacturing are addressed, and continuous production is discussed as a potential solution. Finally, potential critical quality attributes are introduced, which may facilitate the optimization of process parameters.
Topics: Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Compounding; Drug Liberation; Microspheres; Molecular Weight; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 34180769
DOI: 10.1080/10717544.2021.1943056 -
Acta Biomaterialia Jul 2020Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during...
Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during regeneration, this necessitates composite systems in which the mechanics of the implant are decoupled from the drug release profile. To address this need, we developed a system in which microspheres (MS) were sequestered in a defined location between two nanofibrous layers. This bilayer delivery system (BiLDS) enables simultaneous structural support and decoupled release profiles. To test this new system, PLGA (poly-lactide-co-glycolic acid) microspheres were prepared using a water-in-oil-in-water (w/o/w) emulsion technique and incorporated Alexa Fluor-tagged bovine serum albumin (BSA) and basic fibroblast growth factor (bFGF). These MS were secured in a defined pocket between two polycaprolactone (PCL) nanofibrous scaffolds, where the layered scaffolds provide a template for new tissue formation while enabling independent and local release from the co-delivered MS. Scanning electron microscopy (SEM) images showed that the assembled BiLDS could localize and retain MS in the central pocket that was surrounded by a continuous seal formed along the margin. Cell viability and proliferation assays showed enhanced cell activity when exposed to BiLDS containing Alexa Fluor-BSA/bFGF-loaded MS, both in vitro and in vivo. MS delivered via the BiLDS system persisted in a localized area after subcutaneous implantation for at least 4 weeks, and bFGF release increased colonization of the implant. These data establish the BiLDS technology as a sustained in vivo drug delivery platform that can localize protein and other growth factor release to a surgical site while providing a structural template for new tissue formation. STATEMENT OF SIGNIFICANCE: Localized and controlled delivery systems for the sustained release of drugs are essential. Many strategies have been developed for this purpose, but most rely on degradation (and loss of material properties) for delivery. Here, we developed a bilayer delivery system (BiLDS) that decouples the physical properties of a scaffold from its delivery kinetics. For this, biodegradable PLGA microspheres were sequestered within a central pocket of a slowly degrading nanofibrous bilayer. Using this device, we show enhanced cell activity with FGF delivery from the BiLDS both in vitro and in vivo. These data support that BiLDS can localize sustained protein and biofactor delivery to a surgical site while also serving as a mechanical scaffold for tissue repair and regeneration.
Topics: Drug Delivery Systems; Drug Liberation; Lactic Acid; Microspheres; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 32428684
DOI: 10.1016/j.actbio.2020.04.048 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Nov 2017To review the research progress of growth factor sustained-release microspheres in fat transplantation. (Review)
Review
OBJECTIVE
To review the research progress of growth factor sustained-release microspheres in fat transplantation.
METHODS
The recently published 1iterature at home and abroad related the growth factor sustained-release microspheres in fat transplantation was reviewed and analyzed.
RESULTS
The sustained-release microsphere carrier materials include natural polymer materials and synthetic polymer materials.The sustained-release complexes of different microsphere materials with different growth factors can promote the vascularization of transplanted fat in a timely manner, improve the survival rate of grafts, and reduce the incidence of complications such as liquefaction, calcification, and necrosis.
CONCLUSION
The growth factor sustained-release microspheres have the characteristics of persistence and controllability, which is a research hotspot in the field of fat transplantation and has broad application prospects.
Topics: Adipose Tissue; Delayed-Action Preparations; Intercellular Signaling Peptides and Proteins; Microspheres; Polymers
PubMed: 29798599
DOI: 10.7507/1002-1892.201703125 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Aug 2023To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then...
OBJECTIVE
To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and and biological properties.
METHODS
Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the "click chemistry" method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination.
RESULTS
The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (<0.05). experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (<0.05).
CONCLUSION
HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
Topics: Animals; Rats; Matrix Metalloproteinase 13; Microspheres; Hydrogels; Collagen Type II; Diclofenac; Inflammation; Osteoarthritis, Knee; Hyaluronic Acid; Aggrecans
PubMed: 37586790
DOI: 10.7507/1002-1892.202302105 -
Chemical Society Reviews Aug 2015Spectrometrically or optically encoded microsphere based suspension array technology (SAT) is applicable to the high-throughput, simultaneous detection of multiple... (Review)
Review
Spectrometrically or optically encoded microsphere based suspension array technology (SAT) is applicable to the high-throughput, simultaneous detection of multiple analytes within a small, single sample volume. Thanks to the rapid development of nanotechnology, tremendous progress has been made in the multiplexed detecting capability, sensitivity, and photostability of suspension arrays. In this review, we first focus on the current stock of nanoparticle-based barcodes as well as the manufacturing technologies required for their production. We then move on to discuss all existing barcode-based bioanalysis patterns, including the various labels used in suspension arrays, label-free platforms, signal amplification methods, and fluorescence resonance energy transfer (FRET)-based platforms. We then introduce automatic platforms for suspension arrays that use superparamagnetic nanoparticle-based microspheres. Finally, we summarize the current challenges and their proposed solutions, which are centered on improving encoding capacities, alternative probe possibilities, nonspecificity suppression, directional immobilization, and "point of care" platforms. Throughout this review, we aim to provide a comprehensive guide for the design of suspension arrays, with the goal of improving their performance in areas such as multiplexing capacity, throughput, sensitivity, and cost effectiveness. We hope that our summary on the state-of-the-art development of these arrays, our commentary on future challenges, and some proposed avenues for further advances will help drive the development of suspension array technology and its related fields.
Topics: Biotechnology; High-Throughput Screening Assays; Microspheres; Nanoparticles; Nanotechnology; Spectrum Analysis
PubMed: 26021602
DOI: 10.1039/c4cs00382a -
Biosensors Feb 2022Suspension microsphere immunoassays are rapidly gaining attention in multiplex bioassays. Accurate detection of multiple analytes from a single measurement is critical...
Suspension microsphere immunoassays are rapidly gaining attention in multiplex bioassays. Accurate detection of multiple analytes from a single measurement is critical in modern bioanalysis, which always requires complex encoding systems. In this study, a novel bioassay with Raman-coded antibody supports (polymer microbeads with different Raman signatures) and surface-enhanced Raman scattering (SERS)-coded nanotags (organic thiols on a gold nanoparticle surface with different SERS signatures) was developed as a model fluorescent, label-free, bead-based multiplex immunoassay system. The developed homogeneous immunoassays included two surface-functionalized monodisperse Raman-coded microbeads of polystyrene and poly(4-tert-butylstyrene) as the immune solid supports, and two epitope modified nanotags (self-assembled 4-mercaptobenzoic acid or 3-mercaptopropionic acid on gold nanoparticles) as the SERS-coded reporters. Such multiplex Raman/SERS-based microsphere immunoassays could selectively identify specific paratope-epitope interactions from one mixture sample solution under a single laser illumination, and thus hold great promise in future suspension multiplex analysis for diverse biomedical applications.
Topics: Gold; Immunoassay; Metal Nanoparticles; Microspheres; Spectrum Analysis, Raman
PubMed: 35200381
DOI: 10.3390/bios12020121 -
Biosensors Sep 2022Neonicotinoids are the most commonly used insecticides due to their effectiveness. However, non-targeted insects, especially bees, are also affected by neonicotinoids....
Neonicotinoids are the most commonly used insecticides due to their effectiveness. However, non-targeted insects, especially bees, are also affected by neonicotinoids. Therefore, neonicotinoid application can contribute to the declining bee populations worldwide. The presented study describes the development of novel competitive, fluorescent microsphere-based suspension immunoassays for neonicotinoid profiling and their application to bees and essential bee-related matrices, using the Multi-Analyte Profiling (xMAP) technology. For the construction of these neonicotinoid microsphere immunoassays (nMIAs), neonicotinoid-ovalbumin conjugates were coupled to unique fluorescent, paramagnetic microspheres, which competed with the free neonicotinoids that were present in test samples for interacting with the corresponding, specific antibodies. In total, five independent nMIA's were developed for the detection of imidacloprid, acetamiprid, clothianidin, thiacloprid, thiamethoxam, dinotefuran, nitenpyram and imidaclothiz with the limits of detection being for 0.01 ng/mL, 0.01 ng/mL, 0.02 ng/mL, 0.02 ng/mL, 0.003 ng/mL, 2.95 ng/mL, 0.09 ng/mL and 0.04 ng/mL, respectively. The developed nMIAs were applied to fortified matrices including surface water, pollen, honey and honeybees. All of the neonicotinoids, except dinotefuran, could be sensitively detected in all of the tested environmental matrices and bees, with there being sensitivities of 1 ng/mL in water and 10 ng/g in solid materials. These nMIAs provide a rapid profiling method for all of the common neonicotinoids, including those that are banned by the European Union for outdoor use. The developed method can contribute to healthy and sustainable beekeeping, globally, via its application in the apiary environment.
Topics: Bees; Animals; Thiamethoxam; Insecticides; Microspheres; Ovalbumin; Neonicotinoids; Water
PubMed: 36290929
DOI: 10.3390/bios12100792 -
Journal of Nanobiotechnology Sep 2023Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of...
Designing a microbial fermentation-functionalized alginate microsphere for targeted release of 5-ASA using nano dietary fiber carrier for inflammatory bowel disease treatment.
Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.
Topics: Humans; Animals; Mice; Microspheres; Fermentation; Irritable Bowel Syndrome; Inflammatory Bowel Diseases; Mesalamine; Alginates; Dietary Fiber
PubMed: 37741962
DOI: 10.1186/s12951-023-02097-6 -
Environmental Health Perspectives Apr 2024Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans...
BACKGROUND
Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored.
OBJECTIVES
This study aims to investigate the impacts of polymer microspheres on tissue metabolism in mice by assessing the microspheres ability to translocate across the gut barrier and enter into systemic circulation. Specifically, we wanted to examine microsphere accumulation in different organ systems, identify concentration-dependent metabolic changes, and evaluate the effects of mixed microsphere exposures on health outcomes.
METHODS
To investigate the impact of ingested microspheres on target metabolic pathways, mice were exposed to either polystyrene () microspheres or a mixture of polymer microspheres consisting of polystyrene (), polyethylene (), and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid) (). Exposures were performed twice a week for 4 weeks at a concentration of either 0, 2, or via oral gastric gavage. Tissues were collected to examine microsphere ingress and changes in metabolites.
RESULTS
In mice that ingested microspheres, we detected polystyrene microspheres in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolic differences that occurred in the colon, liver, and brain, which showed differential responses that were dependent on concentration and type of microsphere exposure.
DISCUSSION
This study uses a mouse model to provide critical insight into the potential health implications of the pervasive issue of plastic pollution. These findings demonstrate that orally consumed polystyrene or mixed polymer microspheres can accumulate in tissues such as the brain, liver, and kidney. Furthermore, this study highlights concentration-dependent and polymer type-specific metabolic changes in the colon, liver, and brain after plastic microsphere exposure. These results underline the mobility within and between biological tissues of MPs after exposure and emphasize the importance of understanding their metabolic impact. https://doi.org/10.1289/EHP13435.
Topics: Humans; Animals; Mice; Polystyrenes; Microspheres; Plastics; Tissue Distribution; Microplastics; Water Pollutants, Chemical
PubMed: 38598326
DOI: 10.1289/EHP13435