Microsphere System Research Articles

Numerical Simulation of the Microscopic Plugging Mechanism and Particle Flow Process of the Microsphere System.

The microsphere system has small initial particle size, excellent swelling performance, simple manufacturing process, and strong plugging ability. It has great application potential in the field of plugging and profile control of deep reservoirs. Microspheres can effectively plug the pores of fractured cores, inhibit the rapid breakthrough process, and improve the sweep efficiency of the injected fluids. However, the microscopic plugging mechanism of microspheres on fractured cores is still unclear. In this study, the distribution of microspheres after plugging was observed through specially prepared core models. Furthermore, the microscopic plugging mechanism of microspheres in fractured reservoir cores was clarified, including direct microsphere plugging, cluster bridging plugging, adhesion plugging, extrusion-deformation plugging, and extrusion-crushing plugging. Then, particle flow simulation software was used to establish the fluid-solid coupling model of microsphere plugging, and then, the numerical simulation of the plugging process was realized by Python module programming. Through this study, the plugging effect of microspheres under different fracture opening conditions was clarified. Moreover, the effects of injection pressure difference, fracture width, and particle size ratio on the fluid-solid structures of microsphere plugging were analyzed. The results show that the smaller the particle size ratio, the greater the injection pressure difference, the fracture width, and the reduction magnitudes in fracture porosity and core permeability and the higher the plugging rate. The numerical simulation results well support the microsphere plugging mechanism obtained by experiments. The results of this study can provide theoretical and technical support for the development of deep profile control and flooding and enhanced oil recovery technology of the polymer microsphere dispersion system in fractured low-permeability reservoirs.

Characterizing the Solvent‐Induced Inversion of Colloidal Aggregation During Electrophoretic Deposition

AbstractElectrophoretic deposition (EPD) of colloidal particles is a practical system for the study of crystallization and related physical phenomena. The aggregation is driven by the electroosmotic flow fields and induced dipole moments generated by the polarization of the electrode‐particle‐electrolyte interface. Here, the electrochemical control of aggregation and repulsion in the electrophoretic deposition of colloidal microspheres is reported. The nature of the observed transition depended on the composition of the solvent, switching from electrode‐driven aggregation in water to electrical field‐driven repulsion in ethanol for otherwise identical systems of colloidal microspheres. This work uses optical microscopy‐derived particles and a recently developed particle insertion method approach to extract model‐free, effective interparticle potentials to describe the ensemble behavior of the particles as a function of the solvent and electrode potential at the electrode interface. This approach can be used to understand the phase behavior of these systems based on the observable particle positions rather than a detailed understanding of the electrode‐electrolyte microphysics. This approach enables simple predictability of the static and dynamic behaviors of functional colloid‐electrode interfaces.

Extended π‑conjugated system of 3D carbon-rich carbon nitride microspheres for boosting photoelectrochemical 4-chlorophenol sensing

4-Chlorophenol (4-CP) is one of the water pollutants with high toxicity and low biodegradability. Accurate detection against 4-CP is of great value to maintain human life. A photoelectrochemical (PEC) sensor based on three-dimensional carbon-rich carbon nitride (named 3D-CN) material was proposed for monitoring 4-CP from water environment. 3D-CN material was prepared by a low-temperature supramolecular self-assembly combined with thermal-polymerization strategy. 3D and carbon rich structure endow 3D-CN material with significantly extended π-conjugated system and enhanced charge mobility, which not only easily activates inherent π → π* electronic transition, but also awakens n → π* electronic transition in 3D-CN material. The n → π* electronic transition can further extend the absorption band edge, results into excellent PEC performance of 3D-CN material. The constructed PEC 4-CP sensor showed excellent selectivity, stability, reproducibility, and accuracy for actual water sample detection. Furthermore, the sensor provided a wide detection range (1.6–3200 μg L–1) and a low limit detection (0.53 μg L–1). This work proposes a new idea for the development of graphitic carbon nitride (g-C3N4) materials with high PEC performance by introducing a synergistic regulation strategy of carbon rich and 3D structure, and broadens the application of g-C3N4-based materials in the field of PEC sensors.

Enzymatic PCL-grafting to NH2-end grouped silica and development of microspheres for pH-stimulated release of a hydrophobic model drug

This study set out to evaluate novel PCL-based silica containing nanohybrids as the polymer matrix in a hydrophobic drug-loaded microsphere system. Nanohybrids were synthesized by PCL-grafting to NH2-end grouped silica by in situ enzymatic ring opening polymerization of ε-caprolactone. Molecular weight and monomer conversion, PCL grafting percentage, thermal properties and crystallinity of the nanohybrids were determined by 1H NMR, TGA, DSC and XRD. Synthesized nanohybrids had low crystallinity percentage (32 and 39 %) and molecular weight (4800 and 8700 g/mol), promising for controlled drug release applications. The nanohybrids were used for fabrication of trans-chalcone-loaded microspheres by O/W single emulsion solvent evaporation. Mean particle diameter of the microspheres were between 15 and 30 µm. The result of release studies showed that optimum microsphere formulations (AP4 and A2, respectively) had 61 and 64 % encapsulation efficiency. One of the more significant findings to emerge from this investigation is that TC release was extended to 16 and 37 days, in a controlled manner. TC release was significantly enhanced in acidic pH media (pH 3.6 and 5.6) indicating pH-dependent release from nanohybrid microspheres; releasing 80–100 % of the loaded drug in 4–14 days. Drug/polymer interactions and molecular structures were investigated by FT-IR spectroscopy and DSC analysis. According to the results obtained, enzymatically synthesized nanohybrids have potential for pH-dependent release of the model drug, trans-chalcone.

Evaluation of the interchangeability between the new fully-automated affinity chrome-mediated immunoassay (ACMIA) and the Quantitative Microsphere System (QMS) with a CE-IVD-certified LC-MS/MS assay for therapeutic drug monitoring of everolimus after solid organ transplantation.

This study aims to evaluate the interchangeability between the Siemens Healthineers' "EVRO" new affinity chrome-mediated immunoassay (ACMIA/EVRO) and Thermo Fisher Scientific's "EVER" Quantitative Microsphere System (QMS/EVER) with Chromsystems' CE-IVD-certified "MassTox" liquid-chromatography/tandem-mass spectrometry (LC-MS/MS) assay for the therapeutic drug monitoring of everolimus. A single lot of reagent, calibrators and controls were used for each assay. A total of 67 whole blood samples (n=67) from patients receiving solid organ transplant were analyzed (n=31 with kidney transplant and n=36 with liver transplant); Passing-Bablok regression and Bland-Altman difference plot were used to evaluate bias and individual agreement; LC-MS/MS analysis was used to measure the actual concentrations of calibrators and controls compared to the assigned value. ACMIA/EVRO did not show any systematic bias compared to LC-MS/MS (intercept=0.244ng/mL, 95% CI:-0.254 to 0.651ng/mL). Nevertheless, significant proportional bias (slope=1.511, 95% CI: 1.420 to 1.619) associated to a combined bias of 44.8% (95% CI: 41.2-48.3%) was observed. Conversely, QMS/EVER did not show any bias at both systematic (intercept=-0.151ng/mL, 95% CI:-0.671 to 0.256ng/mL) and proportional level (slope=0.971, 95% CI: 0.895 to 1.074) with a non-statistically significant combined bias of-3.6% (95% CI:-8.4-1.1%). Based on a concentration of calibrators and controls above the assigned value for both the analytical methods, in the ACMIA/EVRO a correction which was approximately one-third of the correction for the QMS/EVER was observed. ACMIA/EVRO but not QMS/EVER shows a lack of interchangeability with the CE-IVD-certified LC-MS/MS assay. We hypothesize that, as the ACMIA/EVRO uses an anti-sirolimus antibody, the under-corrected assigned value in the assay calibrators was not sufficient to reproduce the everolimus metabolites cross-reactivity occurring in real samples.

Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care.

One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system.

Preparation and characterization of microspheres embedded hydrogels for controlled release of avermectin

In this study, using sodium alginate and chitosan as carrier materials, release- controlled microspheres loaded avermectin were prepared by complex coacervation method, the drug grinding time and sodium alginate concentration were determined, and the drug loading rate and entrapment efficiency of the prepared microspheres were 30.38% and 81.47%, respectively. At the same time, the composite systems of microspheres Impregnated CS-PVA hydrogels were prepared. The influence of pH and temperature on swelling ratio of microspheres and composite systems were determined. Results showed that microspheres and composite systems have good pH and temperature responsive behavior. The release time of avermectin could be prolonged by embedding microspheres into the hydrogels, and the release mechanism of abamectin in microspheres and composite system Ⅲall fit no-Fick diffusion.

Micro Encapsulation and Characterization of Diclosulam in Xanthan Gum Based Polymeric System for Smart Delivery of Herbicide in Crop Production

Aim: Micro encapsulation of diclosulam herbicide was done in xanthan gum based polymeric system through ionotropic gelation method to formulate a slow-release herbicide to achieve prolonged weed control in irrigated upland ecosystem.
 Place and Duration of Study: The slow-release formulation of diclosulam was synthesized and characterized in the Department of Nano Science & Technology, Tamil Nadu Agricultural University during January to July 2022.
 Methodology: Xanthan gum- alginate microsphere system was synthesized with varying concentrations of calcium chloride (CaCl2) (2, 4 and 6 per cent) to encapsulate diclosulam through ionotropic gelation. The size, entrapment efficiency, pore volume, pore radius, surface area and swelling behavior of microspheres were assessed to achieve higher loading of diclosulam and good stability of microspheres.
 Results: The mean diameter of xanthan gum-alginate microsphere was higher with 6 per cent ion gelation bath followed by the concentration of 4 and 2 per cent. Higher entrapment efficiency of diclosulam was achieved with loading of two percent diclosulam in six per cent calcium crosslinked microspheres.
 Conclusion: Xanthan gum-alginate microsphere system offers both burst release and controlled release of active ingredients. However, controlled release polymeric templates with herbicide will synchronize the release of herbicide with the emergence of weeds in the cropped situations for better weed management.

Preparation of uniform-sized GeXIVA[1,2]-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency

The purpose of this study was to prepare GeXIVA[1,2] PLGA microspheres by W/O/W re-emulsification-solvent evaporation technology and to develop sustained-release formulations to meet the clinical treatment needs of chronic neuropathic pain. Through prescription optimization, the uniformity of particle size and the encapsulation efficiency is improved, so as to achieve the quality standard of the microspheres. The mechanism of trehalose improving the stability of GeXIVA[1,2] was studied and verified by molecular simulation. The results showed that when adding trehalose to W1, using the PLGA model of 75:25, PLGA concentration of 30%, PVA concentration of 1.5%, adding 1% NaCl to PVA and adding 1% NaCl to solidification water, the prepared microspheres are smooth, the particle size is about 25 μm, and the encapsulation rate reaches 90%. The results of in vitro release experiments showed that the microspheres could be released steadily for about 30 days. The microsphere samples were characterized and analyzed by molecular simulation and powder X-ray diffractometer, and the protective mechanism of trehalose on GeXIVA[1,2] was discussed. The results showed that the hydrogen bond formed between trehalose and GeXIVA[1,2] acted as a hydration film and played a certain protective role on GeXIVA[1,2]. In addition, high-viscosity trehalose can form a glass state and wrap around GeXIVA[1,2], reducing the free movement of molecules. In the microsphere system, trehalose can also avoid the influence of PLGA material on the secondary structure of GeXIVA[1,2]. In conclusion, this study is expected to provide a new therapeutic strategy for the treatment of chronic neuropathic pain.

Formulation and evaluation of polymeric microspheres of a poorly soluble drug celecoxib

The aim of this present work was to formulate microspheres of BCS Class II drug Celecoxib. The drug was identified by melting point study and FT-IR spectroscopy. Therapeutic success of a drug is greatly depended on its bioavailability. Majority of the recently discovered drugs shows poor solubility (BCS Class II) which decreases the bioavailability upon oral administration. Microspheres are a novel technique to circumvent this obstacle, which can increase bioavailability of drugs significantly. Polymeric microspheres with Polyvinylpyrrolidone and Eudragit L-100, prepared by Emulsion Solvent Diffusion and Evaporation technique, showed a range of drug release profile at intestinal pH 6.8. Different batches of microspheres were prepared by varying the drug-polymer ratio. Microparticulate systems like microspheres improve absorption which increases the bioavailability, ultimately leading to more efficient drug therapy. The microsphere system also provides protection to the gastric mucosa from GIT-irritant drugs thus decreasing toxic effects and sustained releases allows lower dosage frequency. Prepared microspheres were evaluated on various parameters like entrapment efficiency, %yield, particle size, scanning electron microscope analysis, and in-vitro drug release profile. Solid spherical microspheres were produced which showed good entrapment efficiency (43%-91%) and released 70-90% of the drug content in 10hrs.

In vitro-in vivo correlation of PLGA microspheres: Effect of polymer source variation and temperature

Development of Level A in vitro-in vivo correlations (IVIVCs) remains challenging for complex long-acting parenterals, such as poly(lactic-co-glycolic acid) PLGA microspheres. The nature of the PLGA polymer excipient has a dominant influence on the performance of PLGA microspheres. These microsphere systems typically exhibit multiphasic in vitro/in vivo release/absorption characteristics and may also show interspecies differences (animal model versus human data). These issues contribute to the difficulties in the development of IVIVCs for PLGA microsphere systems. To gain a better understanding of how to achieve IVIVCs for PLGA microspheres, microsphere formulations with similar as well as different release characteristics were prepared using PLGAs from different sources. Efforts were then made to establish IVIVCs for these formulations using in vitro release profiles obtained at both 37°C (human body temperature) and 39°C (rabbit body temperature) with in vivo data obtained from an animal model (rabbit). Risperidone was selected as the model drug; microsphere formulations were prepared under the same processing methods using apparently similar PLGAs from different sources. Owning to the different physicochemical properties of the PLGAs (such as inherent viscosity, monomer ratio (L/G ratio) and blockiness), the formulations exhibited significant differences in critical quality attributes (such as particle size, particle size distribution, porosity and pore size) and consequently had different in vitro and in vivo performance. IVIVCs were developed and it was shown that model predictability improved when IVIVCs were established using those formulations with comparable release characteristics. In addition, IVIVCs were established with Tscaling factors close to 1 using in vitro release profiles acquired at 39°C, emphasizing the importance of considering the body temperature in understanding interspecies differences. The present work provides a comprehensive understanding of the impact of the PLGA source variation on IVIVC development and predictability for complex long-acting parenterals such as PLGA microspheres.

Abstract 175: Production of cancer tissue-engineered microspheres for high-throughput screening

Abstract There is a need for new in vitro systems that enable pharmaceutical companies to collect more physiologically-relevant information on drug response in a low-cost and high-throughput manner. For this purpose, three-dimensional (3D) spheroidal models have been established as more effective than two-dimensional models. Current commercial techniques, however, rely heavily on self-aggregation of dissociated cells and are unable to replicate key features of the native tumor microenvironment, particularly due to a lack of control over extracellular matrix components and heterogeneity in shape, size, and aggregate forming tendencies. In this study, we overcome these challenges by coupling tissue engineering toolsets with microfluidics technologies to create engineered cancer microspheres. Specifically, we employ biosynthetic hydrogels composed of conjugated poly(ethylene glycol) (PEG) and fibrinogen protein (PEG-Fb) to create engineered breast and colorectal cancer tissue microspheres for 3D culture, tumorigenic characterization, and examination of potential for high-throughput screening (HTS). MCF7 and MDA-MB-231 cell lines were used to create breast cancer microspheres and the HT29 cell line and cells from a stage II patient-derived xenograft (PDX) were encapsulated to produce colorectal cancer (CRC) microspheres. Using our previously developed microfluidic system, highly uniform cancer microspheres (intra-batch coefficient of variation (CV) ≤ 5%, inter-batch CV < 2%) with high cell densities (>20×106 cells/ml) were produced rapidly, which is critical for use in drug testing. Encapsulated cells maintained high viability and displayed cell type-specific differences in morphology, proliferation, metabolic activity, ultrastructure, and overall microsphere size distribution and bulk stiffness. For PDX CRC microspheres, the percentage of human (70%) and CRC (30%) cells was maintained over time and similar to the original PDX tumor, and the mechanical stiffness also exhibited a similar order of magnitude (103 Pa) to the original tumor. The cancer microsphere system was shown to be compatible with an automated liquid handling system for administration of drug compounds; MDA-MB-231 microspheres were distributed in 384 well plates and treated with staurosporine (1 μM) and doxorubicin (10 μM). Expected responses were quantified using CellTiter-Glo® 3D, demonstrating initial applicability to HTS drug discovery. PDX CRC microspheres were treated with Fluorouracil (5FU) (10 to 500 μM) and displayed a decreasing trend in metabolic activity with increasing drug concentration. Providing a more physiologically relevant tumor microenvironment in a high-throughput and low-cost manner, the PF hydrogel-based cancer microspheres could potentially improve the translational success of drug candidates by providing more accurate in vitro prediction of in vivo drug efficacy. Citation Format: Elizabeth A. Lipke, Wen J. Seeto, Yuan Tian, Mohammadjafar Hashemi, Iman Hassani, Benjamin Anbiah, Nicole L. Habbit, Michael W. Greene, Dmitriy Minond, Shantanu Pradhan. Production of cancer tissue-engineered microspheres for high-throughput screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 175.

Catechol-modified chitosan hydrogel containing PLGA microspheres loaded with triclosan and chlorhexidine: a sustained-release antibacterial system for urinary catheters

Blockage and infection are common in hospitals, especially with long-term indwelling catheters, due to bacterial adhesion, colonization, and other reasons. A drug-sustained-release antibacterial coating for urinary catheters was described in this paper. Chlorhexidine (CHX) and triclosan (TCS) were encapsulated in poly(lactic-co-glycolic acid) microspheres and mixed with a modified chitosan hydrogel deposited on the surface of silicone rubber. The results showed that drugs can be released continuously more than 35 days. Catechol-modified chitosan (Chi-C) hydrogel was successful synthesized according to FT-IR and UV spectrophotometry, as well as 1H NMR. Furthermore, the coating with CHX and TCS presented stable antibacterial ability compared to the other groups. The results of CCK-8 revealed that the coating was cytotoxic-free and had a wide range of applications. The findings could provide a new drug sustained-release system and hydrogel-microsphere assembly for urinary catheters. Highlights The microspheres presented a sustained release more than 40 days with a remarkable initial burst release. The microspheres/catechol-modified chitosan (Chi-C)/silicon rubber system emerged stable binding ability in liquid environment more than 14 days. The Chi-C/chlorhexidine (CHX)+triclosan (TCS) microspheres system presented better antimicrobial property for entire experiment period. The coated samples showed no significant difference for relative growth rate (RGR) compared to different groups.

Mesenchymal Stem Cells-Hydrogel Microspheres System for Bone Regeneration in Calvarial Defects.

The repair of large bone defects in clinic is a challenge and urgently needs to be solved. Tissue engineering is a promising therapeutic strategy for bone defect repair. In this study, hydrogel microspheres (HMs) were fabricated to act as carriers for bone marrow mesenchymal stem cells (BMSCs) to adhere and proliferate. The HMs were produced by a microfluidic system based on light-induced gelatin of gelatin methacrylate (GelMA). The HMs were demonstrated to be biocompatible and non-cytotoxic to stem cells. More importantly, the HMs promoted the osteogenic differentiation of stem cells. In vivo, the ability of bone regeneration was studied by way of implanting a BMSC/HM system in the cranial defect of rats for 8 weeks. The results confirmed that the BMSC/HM system can induce superior bone regeneration compared with both the HMs alone group and the untreated control group. This study provides a simple and effective research idea for bone defect repair, and the subsequent optimization study of HMs will provide a carrier material with application prospects for tissue engineering in the future.

Use of mesoporous polydopamine nanoparticles as a stable drug-release system alleviates inflammation in knee osteoarthritis.

Osteoarthritis drugs are often short-acting; therefore, to enhance their efficacy, long-term, stable-release, drug-delivery systems are urgently needed. Mesoporous polydopamine (MPDA), a natural nanoparticle with excellent biocompatibility and a high loading capacity, synthesized via a self-aggregation-based method, is frequently used in tumor photothermal therapy. Here, we evaluated its efficiency as a sustained and controlled-release drug carrier and investigated its effectiveness in retarding drug clearance. To this end, we used MPDA as a controlled-release vector to design a drug-loaded microsphere system (RCGD423@MPDA) for osteoarthritis treatment, and thereafter, tested the efficacy of the system in a rat model of osteoarthritis. The results indicated that at an intermediate drug-loading dose, MPDA showed high drug retention. Furthermore, the microsphere system maintained controlled drug release for over 28 days. Our in vitro experiments also showed that drug delivery using this microsphere system inhibited apoptosis-related cartilage degeneration, whereas MPDA-only administration did not show obvious cartilage degradation improvement effect. Results from an in vivo osteoarthritis model also confirmed that drug delivery via this microsphere system inhibited cartilage damage and proteoglycan loss more effectively than the non-vectored drug treatment. These findings suggest that MPDA may be effective as a controlled-release carrier for inhibiting the overall progression of osteoarthritis. Moreover, they provide insights into the selection of drug-clearance retarding vectors, highlighting the applicability of MPDA in this regard.

Construction of Unsaturated Collagen Microsphere System Based on Hydrogen/Coordination Bond and Application.

In this paper, unsaturated collagen microspheres (CMA-Cr/ST) were constructed from vinyl collagen (CMA, which is from leather solid waste) and chromium/synthetic tannins (Cr/ST) through hydrogen and coordination bonds and grafted on polyamide nonwoven fiber by thiol-ene click chemistry to improve the moisture absorption and permeability of nonwoven. The results showed that when the quality ratio of CMA to Cr/ST was 1:1, the magnetic stirring time was 20 min with 250 rpm at room temperature, the surface and particle size distribution of the obtained microspheres were smooth and relatively uniform, and the average particle size was 2-3 μm. When the concentrations of the microspheres and the initiators were 6 and 0.006 wt %, the irradiation time was 4 h and the grafting rate of CMA-Cr/ST on the surface of polyamide fibers would reach 31.3%. The moisture absorption and permeability of the obtained microsphere-modified polyamide nonwoven fiber (CMA-Cr/ST-S-PA) were increased. It was found that the collagen microspheres were firmly modified on the polyamide fibers by moisture and heat resistance, wash resistance, and solvent resistance studies.

Electrosprayed Regeneration‐Enhancer‐Element Microspheres Power Osteogenesis and Angiogenesis Coupling

Electrosprayed microspheres for bone regeneration are conventionally restricted by the lack of osteogenic modulation for both encapsulated stem cells and surrounding cells at the defect site. Here, sodium alginate microspheres encapsulating L-arginine doped hydroxyapatite nanoparticles (Arg/HA NPs) and bone mesenchymal stem cells (BMSCs) as regeneration-enhancer-element reservoirs (Arg/HA-SA@BMSC) for bone healing are electrosprayed. The Arg/HA NPs serve as a container of L-arginine and Ca2+ and the BMSCs inside the microspheres metabolize the released L-arginine into bioactive gas nitric oxide (NO) in the presence of Ca2+ to activate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Meanwhile, the generated NO diffuses out of the microspheres together with the Ca2+ and L-arginine as exterior enhancers to promote the osteogenesis-angiogenesis coupling of surrounding BMSCs and endothelial cells (ECs) at the bone defect site, generating an internal/external modulation loop between the encapsulated cells and surrounding native cells. It is demonstrated that such regeneration-enhancer-element reservoirs could effectively increase the bone tissue formation and neovasculature using rat calvarial defect models. It is envisioned that the microsphere system could streamline vascularized bone regeneration therapy as a high throughput, minimally invasive yet highly effective strategy to accelerate bone healing.

The Impact of Microsponge and Microsphere on Improving Oral Bioavailability of Medications: A Short Review

While many diseases require an efficient drug delivery technology that has the ability to improve bioavailability and alleviate side effects, various types of gastroretentive drug delivery systems (GRDDS) have been developed in order to overcome the obstacles, which are related to a narrow absorption window, instability, site of action, side effects, and dosing frequency. In this context, microsponge and microsphere systems depict two different types of GRDDS, aiming to provide adequate time for active ingredients to be absorbed in the stomach despite the variation in releasing mechanisms of the entrapped ingredients. For the successful designing of these systems, it is essential to optimize the characterizations of the formulated microparticles by considering physiological, pharmaceutical, and patient-related factors, which have a dramatic impact on the efficacy. Consequently, they will demonstrate different behaviors at the desired site of action, determining which systems are showing superiority compared to others. However, each microparticle system has some advantages over the others, providing more options for researchers to ease the difficulties that exist with conventional oral dosage forms. Therefore, this review aims to shed the light on critical factors that have significant impacts on microsponge and microsphere systems and addresses their advantages and disadvantages, providing an understanding of these criteria in order to optimize the drug systems.

Optimasi Jumlah Etil Selulosa dan Kecepatan Pengadukan dalam Preparasi Hollow Microspheres Kaptopril

Captopril is an Angiotensin-Converting Enzyme inhibitor (ACE Inhibitor) used for the treatment of hypertension. It has been reported that the duration of antihypertensive action after a single oral dose of captopril is only 6–8 h, specific absorption in the stomach, stable at acidic pH and degraded at high pH. These indicate a promising potential of the captopril hollow microspheres system as an alternative to the conventional dosage form. The preparation method used in this study is non-aqueous solvent evaporation. This study aims to determine the amount of ethyl cellulose (EC) and stirring speed to produce hollow microspheres having entrapment efficiency (EE), buoyancy and particle size maximum. Determination of the optimum hollow formula microspheres captopril uses a design factorial of two factors at two levels. The factors used in this study were the amount of EC and stirring speed, while the observed response was EE, buoyancy and particle size. The chosen optimum formula will be verified and characterized (yield, SEM, FT-IR). Formula AB was the optimum formula with EE 90.68%, buoyancy 81.52% and particle size 267.10µm. The verification obtained results in accordance with the prediction of the Design-Expert software. The characterization results obtained a yield value of 98.33%, with a spherical shape, uneven surface morphology, and hollow core. The results of FT-IR analysis showed that there was no interaction between the drug and polymer used in the formulation.

Microporous hierarchically Zn-MOF as an efficient catalyst for the Hantzsch synthesis of polyhydroquinolines

A three-dimensional walnut-like Zn-based MOF microsphere system was designed and synthesized via hydrothermal reaction of zinc salt with 4,6-diamino-2-pyrimidinethiol as a tridentate ligand. Besides, Zn ions were coordinated to the functional groups of the ligand to give a novel Zn-MOF microsphere material. Afterward, the resultant material was thoroughly characterized using various analysis and physico-chemical methods; including, FT-IR, XRD, TGA, EDX, X-ray mapping, SEM, TEM, and BET analysis. The Zn-MOF microspheres were utilized in the Hantzsch reaction for a selective synthesis of asymmetric polyhydroquinolines, using various aromatic aldehydes. Our strategy aims at providing a controlled synthesis of hierarchically nanoporous Zn-MOF microspheres with a well-defined morphology, structure, and excellent catalytic properties. Besides, it would result in having a promising heterogeneous catalyst for a selective synthesis with good yields, short reaction time, a low limit of steric hindrance and electronic effects. Moreover, the heterogeneity of the catalyst is further tested with hot filtration and also the reusability results point.