Characteristics Of Microspheres Research Articles

Exploring the impact of microfluidic chip structure on the efficacy of three-dimensional tumor microspheres cultivation.

Three-dimensional (3D) tumor microspheres can simulate the interaction and growth dynamics of tumor cells, and have been used as a new in vitro model for drug screening and tumor biology related research. The scaffold-free culture of 3D tumor microspheres on microfluidic chips has many advantages, including low cost, high throughput, convenience and flexibility. However, it is still unclear how various factors, such as chip structure, influence the culture effect of tumor microspheres. The lack of standardized evaluation and characterization of the culture effect hinders the further optimization and development of chip function. This study presents numerical simulations of multiple parts or processes of the proposed 3D culture chips with two different structural parameters based on computational fluid dynamics (CFD) methods. An evaluation system for tumor microspheres was established. The prediction of the CFD simulation was consistent with the culture results of the chips, reflecting the important role of the structural parameters of the microtrap in the formation of uniform tumor microspheres. Furthermore, the velocity of cell suspension also had a significant impact on the retention of tumor cells. Additionally, the drug screening results of tumor microspheres indicated that tumor microspheres exhibit greater drug resistance, which may be attributed to their size. These results offer valuable insights into the factors that influence the characteristics of tumor microspheres. This research provides a reference and direction for the optimal design and functional evaluation of scaffold-free 3D culture chips, and holds promise for promoting the development of novel drug research platforms.

Incorporation of carboxymethyl chitosan (CMCS) for the modulation of physio-chemical characteristics and cell proliferation environment of the composite hydrogel microspheres

Hydrogels have excellent swelling properties and have been widely applied in tissue engineering because of their similarity to the extracellular matrix (ECM). Sodium alginate (SA) and carboxymethyl chitosan (CMCS) were prepared into hydrogel microspheres with Ca2+crosslinking in our study. The morphology, inner structure, mechanical properties, water content, swelling rate and BMP-2 loading and releasing properties were characterized. Our results showed that the composite SA /CMCS hydrogel microspheres were translucent and spherical in shape with uniform particle size. The incorporation of CMCS further increased the diameters of the microspheres, internal pore structure, water content, and mechanical properties of the SA/CMCS hydrogel microspheres. At the same SA concentration, with the increase of CMSC concentration, the diameter of microspheres could be increased by about 0.4 mm, the water content can be increased about 1%-2%. As for the mechanical properties, the compressive strength can be increased by 0.04-0.1 MPa, and the modulus of elasticity can be increased by 0.1-0.15 MPa. BMP-2 was chosen as a model agent and it could be loaded into SA/CMCS microspheres, and the incorporation of CMCS increased BMP-2 loading. The encapsulated BMP-2 was sustainably releasedin vitro. The leaching solutions of the SA/CMCS hydrogel microspheres exhibited good cytocompatibility and could increase ALP activity, ALP expression, and biomineralization on MC3T3-E1 cells. After 7 d of co-culture, ALP activities in S2.5C2 and S2.5C3 groups was increased by 50% and 45% compared with that of the control group. When embedded in the SA/CMCS microspheres, the MC3T3-E1 cells were evenly distributed inside the hydrogel microspheres and remained viable. Transcriptomic studies showed that incorporation of CMCS induced upregulation of 1141 differentially expressed genes (DEGs) and downregulation of 1614 DEGs compared with SA microspheres. The most significantly enriched pathways were the Wnt and MAPK signaling pathways induced by the incorporation of CMCS and BMP-2. In conclusion, our results indicated that the physiochemical characteristics of the SA hydrogel microspheres could be greatly modulated by CMCS to better mimic the ECM microenvironment and induce osteo-inductive activities of MC3T3-E1 cells.

One-step synthesis of versatile PbMoO4@CdMoO4 microspheres hybrid for the enhanced photocatalytic dye degradation

In this work, we have demonstrated the productive synthesis of novel and versatile CdMoO4@PbMoO4 microspheres hybrid photocatalysts by a simple chemical reduction process. Fabricated CdMoO4@PbMoO4 hybrid microsphere characteristics were analyzed by various techniques to ascertain their structural and morphological properties. The photocatalytic degradation properties of CdMoO4@PbMoO4 hybrid microspheres were evaluated against methylene blue (MB) and congo red (CR) colorants under visible light. The hierarchical structure of CdMoO4@PbMoO4 along with the modulated bandgap, interfacial valence state electrons shift, and quick conversion of the Cd2+/Pb2+ cycle led to the display of the 98 % and 97 % degradations of CR and MB under visible light treatment, respectively which is superior to the corresponding pure structures degradation efficiency, signifying their boosted catalytic properties. Furthermore, the degradation mechanism endorsed excellent dye photodegradation under visible light illumination by the novel CdMoO4@PbMoO4 microspheres hybrid catalyst. The observations gave more insight into the progress of the advancement of CdMoO4@PbMoO4 microspheres hybrid to effectively detoxify perilous and toxic water effluents for industrial purposes.

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.

Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

Research Progress on Injectable Microspheres as New Strategies for the Treatment of Osteoarthritis Through Promotion of Cartilage Repair

AbstractOsteoarthritis (OA) is a degenerative disease caused by a variety of factors with joint pain as the main symptom, including fibrosis, chapping, ulcers, and loss of cartilage. Traditional treatment can only delay the progression of OA, and classical delivery system have many side effects. In recent years, microspheres have shown great application prospects in the field of OA treatment. Microspheres can support cells, reproduce the natural tissue microenvironment in vitro and in vivo, and are an efficient delivery system for the release of drugs or biological agents, which can promote cell proliferation, migration, and differentiation. Thus, they have been widely used in cartilage repair and regeneration. In this review, preparation processes, basic materials, and functional characteristics of various microspheres commonly used in OA treatment are systematically reviewed. Then it is introduced surface modification strategies that can improve the biological properties of microspheres and discussed a series of applications of microsphere functionalized scaffolds in OA treatment. Finally, based on bibliometrics research, the research development, future potential, and possible research hotspots of microspheres in the field of OA therapy is systematically and dynamically evaluated. The comprehensive and systematic review will bring new understanding to the field of microsphere treatment of OA.

Exploring the Effects of Process Parameters during W/O/W Emulsion Preparation and Supercritical Fluid Extraction on the Protein Encapsulation and Release Properties of PLGA Microspheres.

In this study, protein-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared via supercritical fluid extraction of emulsion (SFEE) technology. To understand the correlation between process parameters and the main quality characteristics of PLGA microspheres, a comprehensive prior study on the influence of process variables on encapsulation efficiency (EE), initial drug burst release (IBR), morphology, surface property, and particle size distribution (PSD) was conducted within a wide process condition range of each unit process step, from the double-emulsion preparation step to the extraction step. Bovine serum albumin (BSA), a high-molecular weight-protein that is difficult to control the IBR and EE of PLGA microspheres with, was used as a model material. As double-emulsion manufacturing process parameters, the primary (W/O) and secondary emulsion (W/O/W) homogenization speed and secondary emulsification time were evaluated. In addition, the effect of the SFEE process parameters, including the pressure (70-160 bar), temperature (35-65 °C), stirring rate (50-1000 rpm), and flow rate of supercritical carbon dioxide, SC-CO2 (1-40 mL/min), on PLGA microsphere quality properties were also evaluated. An increase in the homogenization speed of the primary emulsion resulted in an increase in EE and a decrease in IBR. In contrast, increasing the secondary emulsification speed resulted in a decrease in EE and an increase in IBR along with a decrease in microsphere size. The insufficient secondary emulsification time resulted in excessive increases in particle size, and excessive durations resulted in decreased EE and increased IBR. Increasing the temperature and pressure of SFEE resulted in an overall increase in particle size, a decrease in EE, and an increase in IBR. It was observed that, at low stirring rates or SC-CO2 flow rates, there was an increase in particle size and SPAN value, while the EE decreased. Overall, when the EE of the prepared microspheres is low, a higher proportion of drugs is distributed on the external surface of the microspheres, resulting in a larger IBR. In conclusion, this study contributes to the scientific understanding of the influence of SFEE process variables on PLGA microspheres.

Enhancing colloid stability of polymer microspheres in water through SiO2 coating: Effects of coating cycles and surface coverage

In this study, we investigated the wettability and agglomeration characteristics of polymer microspheres coated with low-temperature deposited SiO2 in a fluidized bed atomic layer deposition (ALD) setup. Surface characterization revealed the presence of a significant amount of deposited Si-OH groups within the first cycles. A drastic decrease in agglomerate size, water contact angle (WCA), and droplet absorption time of the powder was observed when coating was applied. Furthermore, we observed an increase in the amount of Si-OH present on the particle surface with increasing coating cycles, while no significant improvement in water affinity was found after the first coating cycles. Our findings suggest that surface coverage is the primary factor in improving the colloid stability of particles, coated at low temperatures. The low temperature operation of our system introduced a chemical vapor deposition (CVD) component to our coating process, which allowed full surface coverage to be achieved within the first two coating cycles.

Optical tracking of the heterogeneous solvent diffusion dynamics and swelling kinetics of single polymer microspheres.

The diffusion dynamics of small molecules into polymer entities is crucial for driving their morphology and function, which can be applied to research fields such as optical identification, medical implantation and intelligent sensing platforms. Herein, we demonstrate a nondestructive bright-field imaging strategy to monitor and control the morphology of polymer microspheres by varying the interfacial interaction and diffusion in a penetrant bath. The nanoscale interface movement of single polymer microspheres was tracked and converted into the diameter variation during the swelling event with sub-pixel accuracy, which is consistent with the calculation using Li-Tanaka's kinetic equations. More interestingly, the solvent diffusion dynamics along different directions of one particle are heterogeneous, indicating the non-uniform internal structure of a soft confined assembly. The swelling characteristics of single polymer microspheres can be quantified by this simple imaging strategy, and the transient intermediate swelling states are captured. To model the lifetime and stabilization times of microplastic entities, solvent selectivity and thermodynamic regulation were introduced to obtain the activation energy down to the single micro-entity level. This optical methodology shows capability for decoding the complex diffusion mechanism in polymer entities and provides guidance for the design of drug delivery systems, sensor platforms, and optical responsive materials.

Study of molecular interaction and texture characteristics of hydrocolloid-mixed alginate microspheres: As a shell to encapsulate multiphase oil cores

This work investigates the molecular interaction of hydrocolloids (xanthan gum (XG), hydroxyethyl cellulose (HEC), carbomer (CBM) and hymagic™-4D (HA)) with sodium alginate (SA) in microspheres in detail. The molecular interaction of hydrocolloids with SA are demonstrated by the rheological property analysis of the mixed solutions as well as the morphology structure and texture characteristics studies of the microspheres. It is found that the hydrocolloids (XG, HEC and CBM) with branches or capable to coil are able to form complex networks with SA through molecular interactions which hinders the free diffusion of calcium ions and changes the texture characteristics of microspheres. In addition, the mixed solutions (SA-XG and SA-HEC) with complex networks and do not have a chelating effect on calcium ions are used to form the shell of the microcapsules through droplet microfluidic technology, and stable with soft microcapsules encapsulating multiphase oil cores have been successfully prepared. At the same time, the textural properties of microcapsules are quantized, which are related to human sensory properties. The developed stable and soft microcapsules which have the properties of sensory comfort are expected to be applied in the personal care industry and a variety of fields.

Graphene-Material-Modified PMMA Coated with 1,3,5,7-Tetranitro-1,3,5,7-tetraazacyclooctane

Since the energetic material 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX) has potential safety hazards during its application, it was chosen to solve this problem by coating the surface of HMX through the self-polymerization reaction of methyl methacrylate (MMA). However, its mechanical properties were poor for further application, so graphene oxide (GO), hydroxylated graphene (GO-OH), and reduced graphene oxide (rGO) were chosen to be doped into PMMA for coating modification. The properties were also investigated. The composite microspheres were regular in shape. Furthermore, it was observed that graphene materials were present on the surface of the microspheres, and no crystal transformation of HMX occurred during the process. The thermal stability of the composite microspheres was improved, and the activation energies of the HMX/PMMA/GO, HMX/PMMA/rGO and HMX/PMMA/GO-OH composite microspheres were increased compared with those of the HMX/PMMA microspheres. At the same time, the high-energy dropout characteristics of the composite microspheres were improved, and the impact sensitivity of all microspheres was reduced, compared with that of the HMX/PMMA microspheres. The compressive strength of pillars pressed with composite microspheres increased by 1.91, 0.92 and 3.13 MPa, respectively. The mechanical properties of the composite microspheres were improved. As a result, HMX/PMMA composite microspheres have better properties.

In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics.

To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. SAP-MS (HepaSphere150-200µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). The drug concentration did not change during absorption. The release rates increased for 10min and then came to an equilibrium. The mean amounts of drug absorbed at 180min and mean release rates at 24h were (a) cefazolin: 265.4mg, 64.2%; (b) lidocaine: 19.6mg, 75.6%; (c) iopamidol: 830.2mg, 22.5%; cefazolin: 137.6mg, 21.2%; (d) iopamidol: 1620.6mg, 78.5%; lidocaine: 13.5mg, 81.4%; and (e) iopamidol: 643.7mg, 52.9%; cefazolin: 194.0mg, 51.6%; lidocaine: 5.3mg, 58.4%. The diameter of SAP-MS increased for approximately 15min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.

Fine structural characteristics of the chorionic microspheres on the egg surface of the orb web spider Trichonephila clavata

The eggs laid by the orb web spider Trichonephila clavata must overwinter in bitterly freezing and dry conditions before hatching, but there does not seem to be any protection like a compact silk case covering the entire eggmass. Instead, the surface of the eggmass is completely coated with a milky coating called chorionic microspheres (CM). Therefore, we investigated the fine structural characteristics of CM to demonstrate their ecological importance. Although the diameter of CM in outer eggmass exhibits a significant variation, the chorionic surface is coated with a single layer of CM, characterized by a consistent diameter of approximately 2.3 µm. The surface structure of aggregated CM shows short papillary projections demonstrating segmental adhesion of mucous components. CM is insoluble in water but partially soluble in anhydrous ethanol, and its spherical structure is completely decomposed by hexafluoroisopropanol (HFIP), a strong organic solvent. Since our fine structural observations clearly show that CM is not derived from vitellogenic or choriogenetic processes, the CM adhesive coatings during ovipositional process appears to be equivalent to cocoon silk for various protective functions in silken eggcase.

Investigation on modeling and correlating drug release profiles in the accelerated and real-time conditions to formulate leuprolide acetate-loaded biodegradable microspheres

Leuprolide acetate (LA)-loaded microspheres containing different types of biodegradable poly(lactic-co-glycolic acid) (PLGA) were prepared by using the W/O/W double-emulsion solvent evaporation method. These formulations were characterized in terms of particle size, drug loading capacity and drug release kinetics. According to the data on modelling in vitro drug release profiles in accelerated and real-time conditions, the microspheres containing mainly PLGA (L:G = 50:50) or PLGA (L:G = 75:25) exhibited triphasic or biphasic release profiles, respectively. A good correlation was established between real-time at 37 °C and accelerated at 50 °C release data, suggesting that the accelerated release testing method could be useful for a rapid assessment of the in vitro drug release characteristics of the prepared formulations. The particle size, drug loading capacity and drug release characteristics of LA-PLGA microspheres were proved to be dependent upon PLGA types with different monomer ratios, PLGA molecular weight, and pore-forming agent. With reference to drug release characteristics, our microsphere formulation composed of PLGA 75:25 and ammonium bicarbonate (as a pore-forming agent) was most equivalent to the reference microspheres for 1-month administration.

EFFECT OF PREPARATION TEMPERATURE ON ETHYLCELLULOSE MICROSPHERE PROPERTIES PREPARED BY OIL-IN-OIL EMULSION SOLVENT EVAPORATION PROCESS

The present study aims to formulate ethylcellulose microspheres using the oil-in-oil emulsion solvent evaporation method and judge the outcome of processing temperature on their features. The effects of the evaporation rate of the solvent on the particle properties and drug release characteristics of the microspheres were studied. Here, microspheres were prepared at different processing temperatues, viz., 10 0 C, 25 0 C, and 40 0 C, and their impact on the various characteristics of microspheres like surface topography, micrometrics, yield percent, encapsulation efficiency, in vitro dissolution, Fourier-transform infrared spectroscopy (FTIR) and release kinetics were elaborately studied. The FTIR study revealed that processing temperature did not affect drug-polymer compatibility. The study observed that the processing temperature had a great influence on the various characteristics of the prepared microsphere. It was observed from sieve analysis that the mean particle size of the microsphere increased with an increase in processing temperature, and the SEM study also corroborated the same result. SEM photographs showed processing at a higher temperature resulted in particles with a smooth surface, in contrast to a lower processing temperature that forms a bumpy surface. Furthermore, a higher temperature favoured formulation with a higher entrapment efficiency (94.42 ± 0.9 %) as compared to a lower temperature (85.2 ± 0.72 %). For a noteworthy timeframe, indinavir sulfate frames a solid solution in the ethylcellulose matrix and proceeds with the amorphous state. The results of an in vitro drug dissolution study showed that microspheres formulated at a higher temperature had a more sustaining effect as compared to those formulated at a lower temperature, which may have resulted due to their higher mean particle size. Using the Korsemeyer Peppas power law, it was found that the way drugs are released is controlled by diffusion.

Adsorption Behavior and Adsorption Dynamics of Micrometer-Sized Polymer Microspheres on the Surface of Quartz Sand

The adsorption of polymer microspheres in a stratum can directly affect its action mode and performance in the actual application process. Understanding the adsorption pattern of polymer microspheres and their adsorption mechanism can facilitate optimization of the application mode and enhance the use efficiency. Ultraviolet spectrophotometry was employed to measure the static adsorption characteristics of polymer microspheres (PMS) on the surface of quartz sand. The PMS adsorption capacity on the surface of quartz sand increased with increasing concentration. When the concentration was 1000 mg/L, the static equilibrium adsorption capacity was 402 μg/g, and monolayer adsorption was dominant. The effect of the contact time on the adsorption was investigated, and the fitting was performed using the isothermal adsorption thermodynamic equilibrium model and the adsorption kinetic model. The adsorption of 800 mg/L PMS tended to equilibrate after 0.8 h of adsorption on the surface of quartz sand, and the adsorption of 1400 mg/L PMS tended to equilibrate after 1 h of adsorption on the surface of quartz sand. Good fitting results of the kinetic adsorption process were obtained using the pseudo-first-order (PFO) model, pseudo-second-order (PSO) model, Elovich model, and mixed-order (MO) model. The effects of the temperature, particle size of the quartz sand, solid–liquid ratio, and salinity on the adsorption of PMS on the surface of quartz sand were examined. The PMS adsorption capacity on the surface of quartz sand decreased with increasing environmental temperature. The adsorption of PMS at the solid–liquid interface was an exothermic process, and the enthalpy of adsorption was negative. As the mass of the quartz sand in the solid–liquid ratio increased, the adsorption capacity decreased; a low salinity and neutral pH were conducive to the adsorption of PMS on the surface of quartz sand.

Investigation of Lyophilized Microspheres Loaded with Leuprolide Acetate

Abstract: Leuprolide acetate (LA) - a nonapeptide, used for the treatment of some hormone-depending diseases, is unstable and very susceptible to degradation in the aqueous media. Poly (lactic-co-glycolic) acid (PLGA) is a copolymer of lactide and glycolide, that has generated tremendous interest in pharmaceutics because of their excellent biocompatibility, biodegradability, and mechanical strength. PLGA is used for the preparation of biocompatible biodegradable extended-release microspheres. However, the PLGA undergoes hydrolytic degradation in an aqueous environment through cleavage of its backbone ester linkages. As a consequence, PLGA-based microspheres loaded with LA are usually lyophilized to ensure the stability of LA and PGLA and reduce agglomeration, sedimentation, and size change of microspheres during storage. The aim of this present study is to evaluate the influence of lyoprotectants namely mannitol, trehalose, lactose, and saccharose on the stability of LA and characteristics of PLGA-based microspheres loaded with LA upon lyophilization. DSC and FTIR were used to evaluate the biocompatibility of LA and lyoprotectants. The results showed that there was no incompatibility between the LA and lyoprotectants. Mannitol solution 1.25% was used in freeze-drying PLGA-based microspheres loaded with LA. The obtained lyophilized microspheres had a good appearance and low moisture. Lyophilized microspheres after reconstitution had no significant change in drug content, size, and size distribution in comparison to that before freeze-drying.
 Keywords: Leuprolide acetate, PGLA, lyophilized, stability, biodegradable microspheres.
 

Characteristics of hollow glass microspheres and design of light polymer composite materials of different composition and dispersed structure

Currently, to obtain light polymer composite materials with high strength characteristics, hollow microspheres of various nature (glass, quartz, polymer, etc.) are used as fillers. Hollow glass microspheres of different grades (manufactured by JSC «SIO Stekloplastik») were studied by various methods, the disperse structure was described using the generalized parameters model, the light dispersion-filled polymer composite materials (DFPCM) were classified according to the structural principle, generalized and reduced parameters were calculated, and the structure, compositions of light CMs on polymer matrices of various nature were designed.

Optimization of Freeform Reversible Embedding of Suspended Hydrogel Microspheres for Substantially Improved Three-Dimensional Bioprinting Capabilities.

Three-dimensional (3D) bioprinting demonstrates technology that is capable of producing structures comparable to native tissues in the human body. The freeform reversible embedding of suspended hydrogels (FRESH) technique involves hydrogel-based bio-inks printed within a thermo-reversible support bath to provide mechanical strength to the printed construct. Smaller and more uniform microsphere sizes of FRESH were reported to aid in enhancing printing resolution and construct accuracy. Therefore, we sought to optimize the FRESH generation protocol, particularly by varying stir speed and stir duration, in hopes to further improve microsphere size and uniformity. We observed optimal conditions at a stir speed of 600 rpm and stir duration for 20 h that generated the smallest microspheres with the best uniformity. Comparison of using the optimized FRESH to the commercial FRESH LifeSupport to bioprint single filament and geometrical constructs revealed reduced single filament diameters and higher angular precision in the optimized FRESH bio-printed constructs compared with those printed in the commercial FRESH. Overall, our refinement of the FRESH manufacturing protocol represents an important step toward enhancing 3D bioprinting resolution and construct fidelity. Improving such technologies allows for the fabrication of highly accurate constructs with anatomical properties similar to native counterparts. Such work has significant implications in the field of tissue engineering for producing accurate human organ model systems. Impact statement Freeform reversible embedding of suspended hydrogels (FRESH) is a method of sacrificial three-dimensional (3D) bioprinting that offers support to reinforce bio-ink extrusion during printing. During FRESH generation, the stir speed and stir duration of the mixture can significantly impact FRESH microsphere characteristics. In this study, we optimized FRESH microspheres to significantly improve resolution and accuracy in bioprinting. This advancement in FRESH-based 3D bioprinting technologies allows for the fabrication of highly accurate constructs with anatomical properties similar to native counterparts and has significant implications in the field of tissue engineering and translational medicine.

Engineered PLGA microspheres for extended-release of naltrexone: in vitro, in vivo, and IVIVR

Poly(lactide-co-glycolide) (PLGA)-based formulation is one of the most often used parenteral extended-release forms to deliver various therapeutics. VIVITROL® as a commercialized PLGA microsphere formulation encapsulates naltrexone, a narcotic antagonist for opioid addiction and alcohol dependency. However, no U.S. Food and Drug Administration-approved generic product of naltrexone PLGA microsphere formulation has entered the market. The availability of generic naltrexone PLGA microspheres in low-income countries will broaden patients’ accessibility to the safe, effective, and more affordable drug. A major challenge in developing such generic forms is the sensitivity of the drug-loaded microspheres’ critical characteristics to the small manufacturing changes, even in formulations with the same compositions as the reference product. In this study, we evaluated the different key manufacturing parameters on the physicochemical, in vitro and in vivo release characteristics of naltrexone microspheres to develop a generic form of naltrexone PLGA microspheres. The selected formulations demonstrated a significant similarity in physicochemical characteristics and release profiles (f2 > 50) to the reference product, VIVITROL®. A strong relationship was observed between in vitro release profile of naltrexone as against its corresponding in vivo profile. It helped to roughly predict the in vivo release behavior of the different manufactured formulations by their corresponding in vitro release profiles.