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International Journal of Nanomedicine 2024As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses.... (Review)
Review
As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.
Topics: Humans; Intervertebral Disc Degeneration; Drug Delivery Systems; Animals; Nanoparticles; Hydrogels; Intervertebral Disc; Reactive Oxygen Species
PubMed: 38813390
DOI: 10.2147/IJN.S463939 -
Oncology Letters Jul 2024Leuprorelin acetate microspheres, a common gonadotropin-releasing hormone agonist, have certain clinical benefits for prostate cancer (PCa). The present study aimed to...
Leuprorelin acetate microspheres, a common gonadotropin-releasing hormone agonist, have certain clinical benefits for prostate cancer (PCa). The present study aimed to compare the efficacy and safety of generic and branded leuprorelin acetate microspheres in patients with PCa. The present retrospective, observational study included 116 patients with PCa who received generic (Boennuokang; Beijing Biote Pharmaceutical Co., Ltd.) or branded (Enantone; Takeda Pharmaceutical Company, Ltd.) leuprorelin acetate microspheres via injection (commonly 3.75 mg once every 4 weeks), defined as the test (n=64) and reference (n=52) groups, respectively. The present study showed that testosterone levels at month (M) 3 (P<0.001), M6 (P=0.012) and M12 (P<0.001) were decreased in the test group compared with the reference group. However, prostate-specific antigen (PSA) levels at baseline, M1, M3, M6 and M12 were not significantly different between the test and reference groups (all P>0.05). The median (interquartile range) testosterone and PSA levels at M12 were 15.50 ng/dl (10.00-31.25 ng/dl) and 0.01 ng/ml (0.01-0.10 ng/ml), respectively, in the test group and 28.00 ng/dl (22.00-37.00 ng/dl) and 0.02 ng/ml (0.01-0.16 ng/ml), respectively, in the reference group. No significant differences were observed in the M1-baseline, M3-baseline, M6-baseline and M12-baseline changes of testosterone or PSA levels between the two groups (all P>0.050). Additionally, the incidence of all adverse events was not significantly different between the two groups (all P>0.050). Overall, Boennuokang leuprorelin acetate microspheres exhibited a similar efficacy for suppression of testosterone and PSA levels with a comparable safety profile compared with Enantone leuprorelin acetate microspheres in patients with PCa.
PubMed: 38807677
DOI: 10.3892/ol.2024.14452 -
Light, Science & Applications May 2024As semiconductor devices shrink and their manufacturing processes advance, accurately measuring in-cell critical dimensions (CD) becomes increasingly crucial....
As semiconductor devices shrink and their manufacturing processes advance, accurately measuring in-cell critical dimensions (CD) becomes increasingly crucial. Traditional test element group (TEG) measurements are becoming inadequate for representing the fine, repetitive patterns in cell blocks. Conventional non-destructive metrology technologies like optical critical dimension (OCD) are limited due to their large spot diameter of approximately 25 μm, which impedes their efficacy for detailed in-cell structural analysis. Consequently, there is a pressing need for small-spot and non-destructive metrology methods. To address this limitation, we demonstrate a microsphere-assisted hyperspectral imaging (MAHSI) system, specifically designed for small spot optical metrology with super-resolution. Utilizing microsphere-assisted super-resolution imaging, this system achieves an optical resolution of 66 nm within a field of view of 5.6 μm × 5.6 μm. This approach effectively breaks the diffraction limit, significantly enhancing the magnification of the system. The MAHSI system incorporating hyperspectral imaging with a wavelength range of 400-790 nm, enables the capture of the reflection spectrum at each camera pixel. The achieved pixel resolution, which is equivalent to the measuring spot size, is 14.4 nm/pixel and the magnification is 450X. The MAHSI system enables measurement of local uniformity in critical areas like corners and edges of DRAM cell blocks, areas previously challenging to inspect with conventional OCD methods. To our knowledge, this approach represents the first global implementation of microsphere-assisted hyperspectral imaging to address the metrology challenges in complex 3D structures of semiconductor devices.
PubMed: 38806499
DOI: 10.1038/s41377-024-01469-3 -
Journal of Nanobiotechnology May 2024By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing...
By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K (SL) K (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.
Topics: Magnetic Resonance Imaging; Gadolinium; Microspheres; Animals; Alginates; Hydrogels; Contrast Media; Wound Healing; Cross-Linking Reagents; Gelatin; Mice; Tissue Scaffolds
PubMed: 38802863
DOI: 10.1186/s12951-024-02549-7 -
Scientific Reports May 2024The fourth phase of water has garnered increased attention within the scientific community due to its distinct properties that differentiate it from regular water. This...
The fourth phase of water has garnered increased attention within the scientific community due to its distinct properties that differentiate it from regular water. This unique state seems to arise potentially from a liquid crystalline structure, which has been observed near various hydrophilic surfaces to possess the capability of excluding microspheres. Consequently, it has been labeled as exclusion zone (EZ) water. When in contact with hydrophilic surfaces, water could exhibit the ability to form organized layers of EZ water. In this study, we investigated the quick buildup of EZ water exposed to xylem vessels of four vegetable plants: cabbage, celery, asparagus, and pumpkin. Among them, pumpkin vessels showed larger EZs, up to 240 ± 56 μm in width. The width of EZ water found near the xylem vessels of the other plants ranged from 133 ± 22 to 142 ± 20 μm. EZ water generally excludes a wide range of particles, including polystyrene microspheres with various surface modifications, as well as silica microspheres. This implies that the formation of EZ water is not an artificial result of using specific microsphere types but rather demonstrates EZ's ability to exclude particles regardless of their composition. Inside single xylem vessels of the pumpkin, we could observe the dynamics of EZ buildup, growing from the inside edge of the vessel toward the center. The relationship between vessel diameter, vessel length, and salt concentration on EZ generation inside the xylem vessel was also explored. The results showed that EZ water can build up both inside and outside the xylem vessels. Our findings suggest that EZ generation inside xylem vessels is associated with water flow, likely driven by a proton gradient. Further research is warranted to elucidate the role of EZ water in the physiology of living plants, particularly considering the limitations of the current experiments conducted on cut-out xylem vessel samples.
Topics: Xylem; Water; Hydrophobic and Hydrophilic Interactions
PubMed: 38802675
DOI: 10.1038/s41598-024-62983-3 -
Journal of Geriatric Cardiology : JGC Apr 2024Coronary artery perforation (CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the...
Coronary artery perforation (CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.
PubMed: 38800547
DOI: 10.26599/1671-5411.2024.04.002 -
International Journal of Pharmaceutics:... Jun 2024The contributions of fine excipient materials to drug dispersibility from carrier-based dry powder inhalation (DPI) formulations are well recognized, although they are...
The contributions of fine excipient materials to drug dispersibility from carrier-based dry powder inhalation (DPI) formulations are well recognized, although they are not completely understood. To improve the understanding of these contributions, we investigated the influences of the particle size of the fine excipient materials on characteristics of carrier-based DPI formulations. We studied two particle size grades of silica microspheres, with volume median diameters of 3.31 μm and 8.14 μm, as fine excipient materials. Inhalation formulations, each composed of a lactose carrier material, one of the fine excipient materials (2.5% or 15.0% /), and a drug (fluticasone propionate) material (1.5% /) were prepared. The physical microstructure, the rheological properties, the aerosolization pattern, and the aerodynamic performance of the formulations were studied. At low concentration, the large silica microspheres had a more beneficial influence on the drug dispersibility than the small silica microspheres. At high concentration, only the small silica microspheres had a beneficial influence on the drug dispersibility. The results reveal influences of fine excipient materials on mixing mechanics. At low concentration, the fine particles improved deaggregation and distribution of the drug particles over the surfaces of the carrier particles. The large silica microspheres were associated with a greater mixing energy and a greater improvement in the drug dispersibility than the small silica microspheres. At high concentration, the large silica microspheres kneaded the drug particles onto the surfaces of the carrier particles and thus impaired the drug dispersibility. As a critical attribute of fine excipient materials in carrier-based dry powder inhalation formulations, the particle size demands robust specification setting.
PubMed: 38799178
DOI: 10.1016/j.ijpx.2024.100251 -
Biological & Pharmaceutical Bulletin 2024Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as...
Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as ophthalmic suspensions. In addition to low bioavailability, suspensions exhibit limited efficacy, safety, and usability due to the presence of drug particles. Improving bioavailability can reduce the drug concentrations and the risk of problems associated with suspended drug particles. However, practical penetration enhancers capable of improving bioavailability remain elusive. Herein, we focused on penetratin (PNT), a cell-penetrating peptide (CPP) that promotes active cellular transport related to macromolecule uptake, such as micropinocytosis. According to the in vitro corneal uptake study using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24, PNT enhanced the uptake of Fluoresbrite YG carboxylate polystyrene microspheres without covalent binding. In an ex vivo porcine eye model, the addition of 10 µM PNT to rebamipide ophthalmic suspension markedly improved the corneal uptake of rebamipide; however, the addition of 100 µM PNT was ineffective due to potentially increased particle size by aggregation. This article provides basic information on the application of PNT as a penetration enhancer in ophthalmic suspensions, including the in vitro and ex vivo studies mentioned above, as well as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and storage stability at different pH values.
Topics: Animals; Cell-Penetrating Peptides; Ophthalmic Solutions; Humans; Cornea; Suspensions; Swine; Quinolones; Administration, Ophthalmic; Biological Availability; Epithelium, Corneal; Particle Size; Alanine
PubMed: 38797668
DOI: 10.1248/bpb.b24-00077 -
International Journal of Biological... Jun 2024Monoclonal antibodies (mAbs) have garnered substantial attention within the field of ophthalmology and can be used to suppress scar formation after minimally invasive...
Monoclonal antibodies (mAbs) have garnered substantial attention within the field of ophthalmology and can be used to suppress scar formation after minimally invasive glaucoma surgeries. Here, by controlling mAb passive diffusion, we developed a polymeric, rate-controlling membrane reservoir loaded with poly(lactic-co-glycolic acid) microspheres to deliver mAb for several weeks. Different parameters were tested to ensure that the microspheres achieved a good quality characteristic, and our results showed that 1 %W/V emulsifier with 5 %W/V NaCl achieved mAb-loaded microspheres with the highest stability, encapsulation efficiency and minimal burst release. Then, we fabricated and compared 10 types of microporous films based on polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG). Our results revealed distinct pore characteristics and degradation patterns in different films due to varying polymer properties, and all the polymeric film formulations showed good biocompatibility in both human trabecular meshwork cells and human conjunctival fibroblasts. Finally, the optimized microspheres were loaded into the reservoir-type polymeric implant assembled by microporous membranes with different surface coating modifications. The implant formulation, which was fabricated by 60 PCL: 40 PEG (3 %W/V) polymer with 0.1 %W/V poly(lactic-co-glycolic acid) barrier, exerted the best drug release profile that can sustained release mAb (83.6 %) for 4 weeks.
Topics: Humans; Glaucoma; Antibodies, Monoclonal; Microspheres; Minimally Invasive Surgical Procedures; Polylactic Acid-Polyglycolic Acid Copolymer; Polyesters; Drug Delivery Systems; Drug Liberation; Polymers; Polyethylene Glycols; Porosity; Drug Carriers
PubMed: 38797299
DOI: 10.1016/j.ijbiomac.2024.132655 -
Scientific Reports May 2024Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules,...
Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules, decellularized extracellular matrix (ECM) may trigger and enhance stem cell proliferation and differentiation. Here, we investigated the controlled release of transforming growth factor beta (TGF-β1) as an active mediator of mesenchymal stromal cells (MSCs) in a biocompatible scaffold and mechanical stimulation for cartilage tissue engineering. ECM-derived hydrogel with TGF-β1-loaded alginate-based microspheres (MSs) was created to promote human MSC chondrogenic development. Ex vivo explants and a complicated multiaxial loading bioreactor replicated the physiological conditions. Hydrogels with/without MSs and TGF-β1 were highly cytocompatible. MSCs in ECM-derived hydrogel containing TGF-β1/MSs showed comparable chondrogenic gene expression levels as those hydrogels with TGF-β1 added in culture media or those without TGF-β1. However, constructs with TGF-β1 directly added within the hydrogel had inferior properties under unloaded conditions. The ECM-derived hydrogel group including TGF-β1/MSs under loading circumstances formed better cartilage matrix in an ex vivo osteochondral defect than control settings. This study demonstrates that controlled local delivery of TGF-β1 using MSs and mechanical loading is essential for neocartilage formation by MSCs and that further optimization is needed to prevent MSC differentiation towards hypertrophy.
Topics: Alginates; Microspheres; Tissue Engineering; Humans; Bioreactors; Hydrogels; Mesenchymal Stem Cells; Chondrogenesis; Animals; Cartilage; Tissue Scaffolds; Decellularized Extracellular Matrix; Transforming Growth Factor beta1; Cell Differentiation; Cells, Cultured; Transforming Growth Factor beta; Extracellular Matrix
PubMed: 38796487
DOI: 10.1038/s41598-024-62474-5