Intervention-Free Graphitization of Carbon Microspheres from a Non-Graphitizing Polymer at Low Temperature: Nanopores as Dynamic Nanoreactors.

Graphitizability of organic precursors is the topic of numerous investigations due to the wide applications of graphitic materials in the industry and emerging technologies of supercapacitors, batteries, etc. Most polymers, such as polydivinyl benzene (PDVB) are classified as non-graphitizings that do not convert to Graphite even after heating to 3000℃. Here, for the first time, the development of graphitic structure in the hierarchal porous sulfonated-PDVB microspheres without employing specific equipment or additives like metal catalysts, organic ingredients, or graphite particles, at 1100°C is reported. The abnormal additive-free graphitic structure formation is confirmed by Raman spectroscopy (ID/IG = 0.87), high-resolution transmission electron microscopy (HRTEM), and selected area diffraction patterns (SAED), as well as x-ray diffraction patterns (XRD), while preservation of aromatic compounds from the carbonization is detected by Fourier transform infrared (FTIR) analysis. Polymer evolution from room temperature to 1100°C is also studied by FTIR, Raman spectroscopy, and XRD techniques. Based on the obtained results, it is suggested that the hierarchal and complicated ink-bottle pore network with a high surface area besides super micropores in the sulfonated-PDVB microspheres has served as nano-sized reaction media. These pores, hereafter referred as "dynamic nanoreactors", are expected to have confined the in-situ produced thermal decomposition products containing broken bond benzene rings, while changing dimensionally and structurally during the designed carbonization regime. This confinement has led to the benzene rings fusion at 250°C, a remarkable extension of them at 450°C, their growth to graphene sheets at 900°C and finally, the stacking of curved graphene layers at 1100°C. The results of this research put stress on the capability of nanopores as nanoreactors to facilitate reactions of decomposition products at low temperatures and ambient pressures to form stacked layers of graphene; A transformation that normally requires catalysts and very high pressures for only specific polyaromatic hydrocarbons.

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

Crack-Resistant Si-C Hybrid Microspheres for High-Performance Lithium-Ion Battery Anodes.

To effectively solve the challenges of rapid capacity decay and electrode crushing of silicon-carbon (Si-C) anodes, it is crucial to carefully optimize the structure of Si-C active materials and enhance their electron/ion transport dynamic in the electrode. Herein, a unique hybrid structure microsphere of Si/C/CNTs/Cu with surface wrinkles is prepared through a simple ultrasonic atomization pyrolysis and calcination method. Low-cost nanoscale Si waste is embedded into the pyrolysis carbon matrix, cleverly combined with the flexible electrical conductivity carbon nanotubes (CNTs) and copper (Cu) particles, enhancing both the crack resistance and transport kinetics of the entire electrode material. Remarkably, as a lithium-ion battery anode, the fabricated Si/C/CNTs/Cu electrode exhibits stable cycling for up to 2300 cycles even at a current of 2.0 A g-1, retaining a capacity of ≈700 mAh g-1, with a retention rate of 100% compared to the cycling started at a current of 2.0 A g-1. Additionally, when paired with an NCM523 cathode, the full cell exhibits a capacity of 135 mAh g-1 after 100 cycles at 1.0 C. Therefore, this synthesis strategy provides insights into the design of long-life, practical anode electrode materials with micro/nano-spherical hybrid structures.

The characterization of cell traction force on nonflat surfaces with different curvature by elastic hydrogel microspheres.

It is of great importance to study the detachment/attachment behaviors of cells (cancer cell, immune cell, and epithelial cell), as they are closely related with tumor metastasis, immunoreaction, and tissue development at variety scales. To characterize the detachment/attachment during the interaction between cells and substrate, some researchers proposed using cell traction force (CTF) as the indicator. To date, various strategies have been developed to measure the CTF. However, these methods only realize the measurements of cell passive forces on flat cases. To quantify the active CTF on nonflat surfaces, which can better mimic the in vivo case, we employed elastic hydrogel microspheres as a force sensor. The microspheres were fabricated by microfluidic chips with controllable size and mechanical properties to mimic substrate. Cells were cultured on microsphere and the CTF led to the deformation of microsphere. By detecting the morphology information, the CTF exerted by attached cells can be calculated by the in-house numerical code. Using these microspheres, the CTF of various cells (including tumor cell, immunological cell, and epithelium cell) were successfully obtained on nonflat surfaces with different curvature radii. The proposed method provides a versatile platform to measure the CTF with high precision and to understand the detachment/attachment behaviors during physiology processes.

Quantitative characterization of tumor cell traction force on extracellular matrix by hydrogel microsphere stress sensor.

Cell traction force (CTF) is a kind of active force that is a cell senses external environment and actively applies to the contact matrix which is currently a representative stress in cell-extracellular matrix (ECM) interaction. Studying the distribution and variation of CTF during cell-ECM interaction help to explain the impact of physical factors on cell behaviors from the perspective of mechanobiology. However, most of the strategies of characterizing CTF are still limited by the measurement needs in three-dimensional (3D), quantitative characteristics and in vivo condition. Microsphere stress sensor (MSS) as a new type of technology is capable of realizing the quantitative characterization of CTF in 3D and in vivo. Herein, we employed microfluidic platform to design and fabricate MSS which possesses adjustable fluorescent performances, physical properties, and size ranges for better applicable to different cells (3T3, A549). Focusing on the common tumor cells behaviors (adhesion, spreading, and migration) in the process of metastasis, we chose SH-SY5Y as the representative research object in this work. We calculated CTF with the profile and distribution to demonstrate that the normal and shear stress can determined different cell behaviors. Additionally, CTF can also regulate cell adhesion, spreading, and migration in different cell states. Based on this method, the quantitative characterization of CFT of health and disease cells can be achieved, which further help to study and explore the potential mechanism of cell-ECM interaction.

Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

Nano-Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications.

Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron-scale dimensions, enhancing their role in minimally invasive therapeutic delivery, tissue repair, and regeneration. The recent emergence of nanomaterials has ushered in a revolutionary transformation in the biomedical field, which demonstrates tremendous potential in targeted therapies, biological imaging, and disease diagnostics. Consequently, the integration of advanced nanotechnology promises to trigger a new revolution in the realm of hydrogels. HMs loaded with nanomaterials combine the advantages of both hydrogels and nanomaterials, which enables multifaceted functionalities such as efficient drug delivery, sustained release, targeted therapy, biological lubrication, biochemical detection, medical imaging, biosensing monitoring, and micro-robotics. Here, this review comprehensively expounds upon commonly used nanomaterials and their classifications. Then, it provides comprehensive insights into the raw materials and preparation methods of HMs. Besides, the common strategies employed to achieve nano-micron combinations are summarized, and the latest applications of these advanced nano-micron combined HMs in the biomedical field are elucidated. Finally, valuable insights into the future design and development of nano-micron combined HMs are provided.

Quantum dot fluorescent microsphere-based immunochromatographic strip for detecting PRRSV antibodies.

Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Current vaccine prevention and treatment approaches for PRRS are not adequate, and commercial vaccines do not provide sufficient cross-immune protection. Therefore, establishing a precise, sensitive, simple, and rapid serological diagnostic approach for detecting PRRSV antibodies is crucial. The present study used quantum dot fluorescent microspheres (QDFM) as tracers, covalently linked to the PRRSV N protein, to develop an immunochromatography strip (ICS) for detecting PRRSV antibodies. Monoclonal antibodies against PRRSV nucleocapsid (N) and membrane (M) proteins were both coated on nitrocellulose membranes as control (C) and test (T) lines, respectively. QDFM ICS identified PRRSV antibodies under 10 min with high sensitivity and specificity. The specificity assay revealed no cross-reactivity with the other tested viruses. The sensitivity assay revealed that the minimum detection limit was 1.2 ng/mL when the maximum dilution was 1:2,048, comparable to the sensitivity of enzyme-linked immunosorbent assay (ELISA) kits. Moreover, compared to PRRSV ELISA antibody detection kits, the sensitivity, specificity, and accuracy of QDFM ICS after analyzing 189 clinical samples were 96.7%, 97.9%, and 97.4%, respectively. Notably, the test strips can be stored for up to 6 months at 4 °C and up to 4 months at room temperature (18-25 °C). In conclusion, QDFM ICS offers the advantages of rapid detection time, high specificity and sensitivity, and affordability, indicating its potential for on-site PRRS screening. KEY POINTS: • QDFM ICS is a novel method for on-site and in-lab detection of PRRSV antibodies • Its sensitivity, specificity, and accuracy are on par with commercial ELISA kits • QDFM ICS rapidly identifies PRRSV, aiding the swine industry address the evolving virus.

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas.

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.

Fabrication of quantum dot-immobilized Y2O3 microspheres with effective photoluminescence for cancer radioembolization therapy.

Microspheres composed of Y-containing materials are effective agents for cancer radioembolization therapy using ß-rays. The distribution and dynamics of these microspheres in tissues can be easily determined by providing the microspheres with an imaging function. In addition, the use of quantum dots will enable the detection of microspheres at the individual particle level with high sensitivity. In this study, core - shell quantum dots were bound to chemically modified yttria microspheres under various conditions, and the effect of reaction conditions on the photoluminescence properties of the microspheres was investigated. The quantum dots were immobilized on the surfaces of the microspheres through dehydration - condensation reactions between the carboxy groups of quantum dots and the amino groups of silane-treated microspheres. As the reaction time increased, the photoluminescence peak blue shifted, and the photoluminescence intensity and lifetime decreased. Therefore, a moderate period of the immobilization process was optimal for imparting effective photoluminescence properties. This study is expected to facilitate particle-level tracking of microsphere dynamics in biological tissues for the development of minimally invasive cancer radiotherapy of deep-seated tumors.

We have established a method to immobilize quantum dots on yttria microspheres for cancer radiotherapy and revealed that photoluminescence intensity can be optimized by controlling the immobilization treatment time.

A Review of Microsphere Super-Resolution Imaging Techniques.

Conventional optical microscopes are only able to resolve objects down to a size of approximately 200 nm due to optical diffraction limits. The rapid development of nanotechnology has increased the demand for greater imaging resolution, with a need to break through those diffraction limits. Among super-resolution techniques, microsphere imaging has emerged as a strong contender, offering low cost, simple operation, and high resolution, especially in the fields of nanodevices, biomedicine, and semiconductors. However, this technology is still in its infancy, with an inadequate understanding of the underlying principles and the technology's limited field of view. This paper comprehensively summarizes the status of current research, the advantages and disadvantages of the basic principles and methods of microsphere imaging, the materials and preparation processes, microsphere manipulation methods, and applications. The paper also summarizes future development trends.

Improving the Signal-to-Noise Ratio of Axial Displacement Measurements of Microspheres Based on Compound Digital Holography Microscopy Combined with the Reconstruction Centering Method.

In 3D microsphere tracking, unlike in-plane motion that can be measured directly by a microscope, axial displacements are resolved by optical interference or a diffraction model. As a result, the axial results are affected by the environmental noise. The immunity to environmental noise increases with measurement accuracy and the signal-to-noise ratio (SNR). In compound digital holography microscopy (CDHM)-based measurements, precise identification of the tracking marker is critical to ensuring measurement precision. The reconstruction centering method (RCM) was proposed to suppress the drawbacks caused by installation errors and, at the same time, improve the correct identification of the tracking marker. The reconstructed center is considered to be the center of the microsphere, rather than the center of imaging in conventional digital holographic microscopy. This method was verified by simulation of rays tracing through microspheres and axial moving experiments. The axial displacements of silica microspheres with diameters of 5 µm and 10 µm were tested by CDHM in combination with the RCM. As a result, the SNR of the proposed method was improved by around 30%. In addition, the method was successfully applied to axial displacement measurements of overlapped microspheres with a resolution of 2 nm.

Exploring the cationic surfactant adsorption efficiency at concentrations relative to the critical micelle concentration by SA/SiO2 microspheres.

Studying the adsorption behavior of cationic surfactants can help to develop more effective strategies to limit their dispersion in the environment. However, there have few studies on the adsorption of cationic surfactants from the perspective of critical micelle concentration (CMC). In this study, with cetyltrimethylammonium bromide (CTAB) and octadecyl trimethylammonium bromide (OTAB) serving as the model cationic surfactants, the effect of CMC on the adsorption behavior of cationic surfactant onto the surface of sodium alginate/silica (SA/SiO2) microspheres was systematically revealed. The adsorption mechanism relative to CMC was investigated under different conditions, including surfactant concentration, pH, temperature, and adsorption time. The results suggest that at identical concentrations, the smaller the CMC value of the cationic surfactants, the greater the adsorption amount (qt). qt for CTAB and OTAB were 583.2 and 678.0 mg/g respectively, with the concentration higher than their CMC value. When the concentration was lower than the CMC value of the cationic surfactants, qt for CTAB and OTAB were 123.2 and 138.7 mg/g, respectively. The CMC value of CTAB was lower than that of OTAB under identical conditions, suggesting that the adsorption of cationic surfactants is related to their CMC. These results are beneficial for the removal of cationic surfactants by adsorption methods.

Spherical Binderless 4A/5A Zeolite Assemblies: Synthesis, Characterization, and Adsorbent Applications.

Zeolite microspheres have been successfully applied in commercial-scale separators such as oxygen concentrators. However, further enhancement of their applications is hampered by the post-synthetic shaping process that formulates the zeolite powder into packing-sized spherical bodies with various binders leading to active site blockage and suboptimal performance. Herein, binderless zeolite microspheres with a tunable broad size range from 2 µm to 500 µm have been developed with high crystallinity, sphericity over 92%, monodispersity with a coefficient of variation (CV) less than 5%, and hierarchical pore architecture. Combining precursor impregnation and steam-assisted crystallization (SAC), mesoporous silica microspheres with a wide size range could be successfully transformed into zeolite. For preserved size and spherical morphology, a judicious selection of the synthesis conditions is crucial to ensure a pure phase, high crystallinity, and hierarchical architecture. For the sub-2-µm zeolite microsphere, low-temperature prolonged aging was important so as to suppress external zeolization that led to a large, single macroporous crystal. For the large 500 µm sphere, ultrasound pretreatment and vacuum impregnation were crucial and facilitated spatially uniform gel matrix dispersion and homogenous crystallization. The obtained zeolite 5A microspheres exhibited excellent air separation performance, while the 4A microspheres displayed ammonium removal capabilities. This work provides a general strategy to overcome the existing limitations in fabricating binder-free technical bodies of zeolites for various applications.

Micron-Sized Thiol-Functional Polysilsesquioxane Microspheres with Open and Interconnected Macropores: Preparation, Characterization and Formation Mechanism.

Polysilsesquioxane (PSQ) microspheres have shown promise in many fields, but previous studies about porous PSQ microspheres are scarce. Herein, we fabricated novel micron-sized thiol-functional polysilsesquioxane (TMPSQ) microspheres with open and interconnected macropores by combining inverse suspension polymerization with two-step sol-gel and polymerization-induced phase separation processes, without using phase-separation-promoting additives or sacrificial templates. The chemical composition of the TMPSQ microspheres was confirmed using FTIR and Raman spectroscopy. The morphology of the TMPSQ microspheres was characterized using SEM and TEM. TGA was employed to test the thermal stability of the TMPSQ microspheres. Mercury intrusion porosimetry and nitrogen adsorption-desorption tests were performed to investigate the pore structure of the TMPSQ microspheres. The results showed that the TMPSQ microspheres had open and interconnected macropores with a pore size of 839 nm, and the total porosity and intraparticle porosity reached 70.54% and 43.21%, respectively. The mechanism of porous generation was proposed based on the morphological evolution observed using optical microscopy. The macropores were formed through the following four steps: phase separation (spinodal decomposition), coarsening, gelation, and evaporation of the solvent. The macropores can facilitate the rapid mass transfer between the outer and inner spaces of the TMPSQ microspheres. The TMPSQ microspheres are promising in various fields, such as catalyst supports and adsorbents.

Immobilization of Coprinus comatus with magnetic alginate hydrogel microsphere for improving the antioxidant activity of fermentation products.

Coprinus comatus is an edible mushroom and its fermented product possesses antioxidant activity. In this study, to further enhance the antioxidant activity and improve the reusability of the strain, calcium alginate hydrogel was used as the carrier for embedding and immobilizing Coprinus comatus. The effects of CaCl2 concentration, sodium alginate concentration, microsphere diameter, and the amount of magnetic particle on the antioxidant activity of fermented products were investigated. The results showed that the magnetic immobilized microsphere prepared by 2.50% CaCl2, 2.00% sodium alginate and 0.50% Fe3O4 had the best fermentation antioxidant activity (EC50 was 0.43 ± 0.01 mg/mL) when the diameter was 5 mm, which increased by 24.56% compared to the initial activity. Besides, the microsphere showed strong reusability, the antioxidant activity was still better than the free strain after being used five times. This study not only enhanced the antioxidant activity of Coprinus comatus fermented product through immobilization, but also provided an effective method for microbial fermentation.

Micron-Sized Thiol-Functional Polysilsesquioxane Microspheres with Open and Interconnected Macropores: Effects of the System Composition on the Porous Structure and Particle Size of the Microspheres.

Control of the porous structure and particle size is essential for improving the properties of polysilsesquioxane (PSQ) microspheres. Herein, using the strategy combining inverse suspension polymerization, two-step sol-gel- and polymerization-induced phase separation processes, micron-sized thiol-containing macroporous PSQ (TMPSQ) microspheres with controllable morphologies, adjustable particle diameters (4.9-17.3 µm), and pore sizes (40-3774 nm) were prepared. The morphology and size of the TMPSQ microspheres were characterized by SEM. The mercury intrusion method was employed to analyze the porous structure of the microspheres. The effects of the composition of the sol-gel disperse phase, the mass ratio of the sol-gel disperse phase to the oil continuous phase (WRW/O), and the Span 80 mass content in the oil continuous phase on the morphology, particle diameter and pore size of the TMPSQ microspheres were investigated. Results indicated that the composition of the sol-gel disperse phase determines the morphology and porous structure of the microspheres, and WRW/O and Span 80 content have remarkable impacts on the morphology and particle size of the microspheres. This study is beneficial to the design and fabrication of functional PSQ microspheres with desired properties and promising application prospects.

Particle Size Measurement and Detection of Bound Proteins of Non-Porous/Mesoporous Silica Microspheres by Single-Particle Inductively Coupled Plasma Mass Spectrometry.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used for particle size measurement of diverse types of individual nanoparticles and micrometer-sized carbon-based particles such as microplastics. However, its applicability to the measurement of micrometer-sized non-carbon-based particles such as silica (SiO2) particles is unclear. In this study, the applicability of spICP-MS to particle size measurement of non-porous/mesoporous SiO2 microspheres with a nominal diameter of 5.0 µm or smaller was investigated. Particle sizes of these microspheres were measured using both spICP-MS based on a conventional calibration approach using an ion standard solution and scanning electron microscopy as a reference technique, and the results were compared. The particle size distributions obtained using both techniques were in agreement within analytical uncertainty. The applicability of this technique to the detection of metal-containing protein-binding mesoporous SiO2 microspheres was also investigated. Bound iron (Fe)-containing proteins (i.e., lactoferrin and transferrin) of mesoporous SiO2 microspheres were detected using Fe as a presence marker for the proteins. Thus, spICP-MS is applicable to the particle size measurement of large-sized and non-porous/mesoporous SiO2 microspheres. It has considerable potential for element-based detection and qualification of bound proteins of mesoporous SiO2 microspheres in a variety of applications.

Improvement of liraglutide release from PLGA microspheres by a porous microsphere-gel composite system.

In the current work, we aimed to prepare a liraglutide-loaded porous microsphere-gel composite system. By employing polyethylene glycol (PEG) as a porogenic agent and poly (lactic-co-glycolic acid) copolymer (PLGA) as a carrier, the liraglutide microspheres were prepared and dispersed in a temperature-sensitive gel made of poloxamer 407 (F-127) and poloxamer 188 (F-68), which served as the gel matrix, to construct the composite system. The porous microsphere-gel composite system demonstrated prolonged and steady drug release, with a reduction to 4.7% in the initial release within 1 d, according to data from in vitro release tests. The drug release from the porous microspheres decreased from 53% to 29% during the rapid release phase as the PEG concentration increased and the release rate slowed down. In vivo experiments in rats revealed that the composite system prolonged the release period by about 10 d. The pharmacokinetic parameter AUC0-1 was decreased by 24.78 ng/ml*h, the initial burst release was decreased, and the blood drug concentration fluctuation was lessened. The construction of a porous microsphere-gel composite matrix offers a novel approach to the systems with a sustained, long-lasting release that utilizes rational design.

Injectable testosterone PLGA microsphere with different characteristics: effect of preparation method (paddle mixing versus microfluidic device).

The purpose of this study was to compare the characteristics of testosterone polylactic-co-glycolic (PLGA) microspheres prepared by a paddle mixer or microfluidics device. The comparison was conducted by not only in vitro evaluation but also in vivo evaluation which has not been reported up to date. We discovered that, among the steps in microsphere preparation, the solvent removal process strongly impacted drug content, particle size and surface morphology. Spectroscopic measurements suggested that molecular interactions and crystallinity of the drug incorporated in the microspheres differed. For the drug release profile, although both mixer- and microfluidics-prepared samples showed similar sustained release of the incorporated drug for approximately one month in vitro, they exhibited different plasma concentration profiles in vivo. Together, our findings show that the preparation process, especially the solvent removal process, may affect the physicochemical characteristics of testosterone PLGA microspheres, leading to different in vivo performance.