Microspheres For Controlled Release Research Articles

Fabrication of crosslinked starch microspheres via water-in-water Pickering emulsion and their application in controlled release of Vitamin C

Green technology for the fabrication of bio-degradable microspheres is exciting and needed. In this study, a new water-in-water Pickering emulsion green technology is proposed for the fabrication of the crosslinked starch microspheres with sodium tripolyphosphate as the crosslinker, polyethylene glycol aqueous solution as the continuous phase (PEG phase) and starch aqueous solution as the dispersed phase (starch phase). The factors that affect the morphology and particle sizes of cross-linked starch microspheres are investigated by laser scanning confocal microscope (LCM) and laser particle size analyzer. The results reveal that the particle sizes of crosslinked starch microspheres are increasing with increased starch concentration. The particle sizes of crosslinked starch microspheres show a first increase and then decrease trend with the increase of the concentration of PEG 20,000 in the PEG phase. The hydrophobic nano silica is used as an emulsifier to form water-in-water Pickering emulsion and shows an obvious effect on the morphology of starch microspheres. When the starch concentration is 20.00 wt%, PEG 20000 concentration is 32.56 wt%, the ratio of starch to PEG phase is 0.20 and the amount of silica is 5.00 wt% of starch, starch microspheres with regular shapes are obtained with the size of about 32.30 ± 0.22 µm. The fabricated cross-linked starch microspheres are non-crystalline and show good water and oil absorption performances. The application of fabricated crosslinked starch microspheres in the adsorption and release of Vitamin C is conducted. The maximum adsorption capacity of crosslinked starch microspheres for Vitamin C reaches 309.9 mg/g. Starch microspheres show a controlled release of Vitamin C in water. This study indicated that crosslinked starch microspheres can be fabricated through a green water-in-water Pickering emulsion technology and may find potential applications in degradable controlled-release microspheres.

Design, Development and Evaluation of Tetracycline Controlled Release Microspheres

Microsphere drug delivery methods have been used to boost efficacy, reduce toxicity, and improve patient compliance. Additional benefits of using microspheres to deliver medications include controlled drug release, improved bioavailability, and targeted drug delivery to the desired location. In order to achieve the required therapeutic effect, hydroxypropyl methyl cellulose K4M and sodium alginate are used as a polymer in microsphere delivery system and different concentration of aluminium chloride is used as cross linking agent. The advantage of microsphere formulations over traditional tablet or capsule formulations is that they increase the surface area exposed to the absorption site, boosting medication absorption and reducing drug dose frequency. Tetracycline is a broad-spectrum antibiotic that is frequently used to treat illnesses like pneumonia and respiratory tract infections. The encapsulation effectiveness, particle size, in -vitro release analysis and release kinetics of the microsphere formulations was assessed.

Aqueous remote loading of model cationic peptides in uncapped poly(lactide-co-glycolide) microspheres for long-term controlled release.

Remote loading microencapsulation of peptides into polymer microspheres without organic solvent represents a promising alternative to develop long-acting release depots relative to conventional encapsulation methods. Here, we formulated drug-free microspheres from two kinds of uncapped poly(lactide-co-glycolides) (PLGAs), i.e., ring-opening polymerized Expansorb® DLG 50-2A (50/50, 11.2kDa) and Expansorb® DLG 75-2A (75/25, 9.0kDa), and evaluated their potential capacity to remote-load and control the release of two model peptides, leuprolide and octreotide. Degradation and erosion kinetics, release mechanism, and storage stability was also assessed. As control formulations, peptide was loaded in the same PLGA 75/25 polymer by the conventional double emulsion-solvent evaporation method (W/O/W) and remote loaded in polycondensation poly(lactic-co-glycolic acid) 75/25 (Wako 7515, 14.3kDa). Loading content of 6.7%-8.9% w/w (~ 67%-89% encapsulation efficiency (EE)) was attained for octreotide, and that of 9.5% w/w loading (~ 95% EE) was observed for leuprolide, by the remote loading paradigm. Octreotide and leuprolide were both slowly and continuously released in vitro from the remote-loaded Expansorb® DLG 75-2A MPs for over 56days, which was highly similar to that observed from traditionally-loaded formulations by W/O/W (8.8% loading, 52.8% EE). The faster release kinetics was observed for the faster degrading PLGA 50/50 remote-loaded Expansorb® DLG 50-2A MPs relative to microspheres from the PLGA 75/25 Expansorb® DLG 75-2A. Despite slight differences in degradation kinetics, the release mechanism of octreotide from the Expansorb® microspheres, whether remote loaded or by W/O/W, was identical as determined by release vs. mass loss curves. Octreotide acylation was also minimal (< ~ 10%) for this polymer. Finally, drug-free Expansorb® DLG 75-2A MPs displayed excellent storage stability over 3months. Overall, this work offers support for the use of ring-opening Expansorb® PLGA-based microspheres to remote load peptides to create simple and effective long-acting release depots.

Aqueous remote loading of setmelanotide in poly(lactic-co-glycolic acid) microspheres for long-term obesity treatment

Setmelanotide (Imcivree™) was developed as a daily injectable therapeutic peptide for the treatment of rare forms of syndromic obesity, such as POMC deficiency and leptin receptor deficiency. The important option of poly(lactic-co-glycolic acid) (PLGA) controlled release microspheres has become more attractive for this class of drugs upon the discovery that net positively charged peptides can be remote-loaded rapidly from aqueous peptide solution into blank microspheres at high loading and encapsulation efficiency. Here we sought to remote-load setmelanotide in PLGA microspheres and examine its potential for long-term controlled release and body weight control. The influence of PLGA microsphere porosity was investigated with respect to morphology, drug loading, and in vitro release profiles. Increased density of the microspheres inhibited the progress of encapsulation of the dicationic peptide. A diet-induced obese murine model was then used to determine the pharmacokinetic profile and to evaluate long-term efficacy of an optimal formulation. Remote loaded PLGA formulations encapsulated setmelanotide as high as ∼63% (∼6.3% w/w loading) and exhibited slow and continuous peptide release over ∼6 weeks in vitro largely independent of microsphere porosity. The obtained in vivo release pattern from deconvolution of the pharmacokinetics after subcutaneous microsphere injection was consistent with the in vitro release profile but with a lower initial burst release and overall slightly faster release rate. After a single injection of remote-loaded setmelanotide, continuous long-term inhibition of food intake and body weight control was observed over 17 and 30 days, respectively. The improvement in body weight control over drug-free microsphere vehicle-treated control groups matched the observed PK profile. This study provides the first report of long-acting release formulation for 1-month controlled release of setmelanotide and body weight control in a diet induced obese murine model, and supports the further development of long-acting treatment options for obese patients.

Investigating structural attributes of drug encapsulated microspheres with quantitative X-ray imaging.

The intra-sphere and inter-sphere structural attributes of controlled release microsphere drug products can greatly impact their release profile and clinical performance. In developing a robust and efficient method to characterize the structure of microsphere drug products, this paper proposes X-ray microscopy (XRM) combined with artificial intelligence (AI)-based image analytics. Eight minocycline loaded poly(lactic-co-glycolic acid) (PLGA) microsphere batches were produced with controlled variations in manufacturing parameters, leading to differences in their underlying microstructures and their final release performances. A representative number of microspheres samples from each batch were imaged using high resolution, non-invasive XRM. Reconstructed images and AI-assisted segmentation were used to determine the size distribution, XRM signal intensity, and intensity variation of thousands of microspheres per sample. The signal intensity within the eight batches was nearly constant over the range of microsphere diameters, indicating high structural similarity of spheres within the same batch. Observed differences in the variation of signal intensity between different batches suggests inter-batch non-uniformity arising from differences in the underlying microstructures associated with different manufacturing parameters. These intensity variations were correlated with the structures observed from higher resolution focused ion beam scanning electron microscopy (FIB-SEM) and the in vitro release performance for the batches. The potential for this method for rapid at-line and offline product quality assessment, quality control, and quality assurance is discussed.

Oral pectin/oligochitosan microspheres for colon-specific controlled release of quercetin to treat inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, life quality-reducing disease with no cures available yet. To develop an effective medication suitable for long-term use is an urgent but unmet need. Quercetin (QT) is a natural dietary flavonoid with good safety and multifaceted pharmacological activities against inflammation. However, orally administrated quercetin yields unproductive outcomes for IBD treatment because of its poor solubility and extensive metabolism in the gastrointestinal tract. In this work, a colon-targeted QT delivery system (termed COS-CaP-QT) was developed, of which the pectin (PEC)/Ca2+ microspheres were prepared and then crosslinked by oligochitosan (COS). The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon. The mechanism study showed that QT triggered the Notch pathway to regulate the proliferation of T helper 2 (Th2) cells and group 3 innate lymphoid cells (ILC3s) and the inflammatory microenvironment was remodeled. The in vivo therapeutic results revealed that COS-CaP-QT could relieve the colitis symptoms and maintain the colon length and intestinal barrier integrity.

Controlled Release Levetiracetam Loaded Eudragits Microspheres for Oral Drug Delivery: Preparation and Evaluation

This work aims to prepare controlled release microspheres loaded with levetiracetam (LEV) for oral use that will have a targeted release site, thus reducing dose frequency and improving patient compliance. Levetiracetam is a 2nd generation antiepileptic medication with a T/half-life of 7 hours that is administered twice daily, which makes it suitable for formulation that will reduce dosing intake. The microspheres were prepared by solvent evaporation method using Eudragit E100, L100, and S100 polymers as matrix core polymers at diff erent ratios 1:1, 1:2 and 1:3 with levetiracetam. These polymers have diff erent pH sensitivity profi les, which will aid the release of levetiracetam in a controlled manner along the gastrointestinal tract. The prepared microspheres were evaluated for yield percentage, entrapment effi ciency (EE%), morphological characteristics and in-vitro release profi le. The yield percentage and EE% for the formulation at diff erent ratios ranged from 69–99%. The in-vitro release analysis showed favorable targeted release of the drug at specifi c pH ranges matching specifi c sites in the gastrointestinal tract.

Loading Glyphosate in Attapulgite and Sodium Alginate Hydrogels to Construct pH-Responsive Controlled Release Microsphere for Enhanced Soil Sustained Release

Herein, we constructed the microsphere SAH-Gly by loading glyphosate (Gly) with dopamine-modified attapulgite (DA-Gly) and capsuling in sodium alginate hydrogels. The Gly releasing rate and the hydrogel swelling rate were manifestly increased to the highest of 60 and 26% within 70 and 24 h in alkaline solution (pH = 8.5), respectively, while only 20% Gly releasing rate and less than 15% hydrogel swelling rate were observed in both acidic (pH = 5.5) and neutral solutions (pH = 7.0). The abundant carboxyl groups in SAH-Gly provided the swelling characters through H+ ionization. Both DA-Gly and SAH-Gly enhanced the stability of Gly to ultraviolet rays and temperature variability. The sustained release of Gly from SAH-Gly resulted in its partial absorption in soils. DA-Gly and SAH-Gly released maximum Gly molecular concentrations after 28 and 32 h, respectively, and then degraded completely in 200 h in soil. First-order kinetics showed that the half-life (DT50) of the Gly residue in soil was 65.89 h, while the DT50 values of DA-Gly and SAH-Gly were 31.18 and 66.27 h, respectively, with the following order: DA-Gly < Gly < SAH-Gly. In addition, leaching experiments depicted that SAH-Gly displayed a weaker elution behavior and longer elution time in the upper soil ring of the column. The sustained release behavior of Gly from SAH-Gly in soil could decelerate the degradation, adsorption, and leaching characters of Gly molecular, helping reduce the loss of active Gly and enhancing its sustainable agricultural practice in response to environmental factors.

Semisolid Pharmaceutical Product Characterization Using Non-invasive X-ray Microscopy and AI-Based Image Analytics.

This work reports the use of X-ray microscopy (XRM) imaging to characterize the microstructure of semisolid formulations containing multiple immiscible phases. For emulsion-based semisolid formulations, the disperse phase globule size and its distribution can be critical quality attributes of the product. Optical microscopy and light diffraction techniques are traditionally used to characterize globule size distribution. These techniques are subjected to sample preparation bias and present challenges from matrix interference and data processing. XRM imaging is an emergent technique that when combined with intelligent data processing has been used to characterize microstructures of pharmaceutical dosage forms including oral solid formulations, controlled release microspheres, and lyophilized products. This work described our first attempt to use XRM imaging to characterize two complex emulsion-based semisolid formulations, a petrolatum-based ointment with a dispersed phase comprising a hydrophilic liquid, and an oil-in-water cream. This initial assessment of technology showed that microstructure details such as globule size distribution, volume fraction, spatial distribution uniformity, inter-globule spacing, and globule sphericity could be obtained and parameterized. It was concluded that XRM imaging, combined with artificial intelligence-based image processing is feasible to generate advanced characterization of semisolid formulation microstructure through 3D visualization and parameterization of globule attributes. This technique holds promise to provide significantly richer microstructure details of semisolid formulations. When fully developed and validated, it is potentially useful for quantitative comparison of microstructure equivalence of semisolid formulations.

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues

The major difference between tissue healing and regeneration is the extent of instructional cues available to precisely direct the biological response. A classic example is reparative or osteodentin that is seen in response to physicochemical injury to the pulp-dentin complex. Dentin regeneration can direct the differentiation of dental stem cells using concerted actions of both soluble (biomolecules, agonists, and antagonists) and insoluble (matrix topology) cues. The major purpose of this study was to examine the synergistic combination of two discrete biomaterial approaches by utilizing nanofiber scaffolds in discrete configurations (aligned or random) with incorporated polymeric microspheres capable of controlled release of growth factors. Further, to ensure appropriate disinfection for clinical use, Radio-Frequency Glow Discharge (RFGD) treatments were utilized, followed by seeding with a mesenchymal stem cell (MSC) line. SEM analysis revealed electrospinning generated controlled architectural features that significantly improved MSC adhesion and proliferation on the aligned nanofiber scaffolds compared to randomly oriented scaffolds. These responses were further enhanced by RFGD pre-treatments. These enhanced cell adhesion and proliferative responses could be attributed to matrix-induced Wnt signaling that was abrogated by pre-treatments with anti-Wnt3a neutralizing antibodies. Next, we incorporated controlled-release microspheres within these electrospun scaffolds with either TGF-β1 or BMP4. We observed that these scaffolds could selectively induce dentinogenic or osteogenic markers (DSPP, Runx2, and BSP) and mineralization. This work demonstrates the utility of a novel, modular combinatorial scaffold system capable of lineage-restricted differentiation into bone or dentin. Future validation of this scaffold system in vivo as a pulp capping agent represents an innovative dentin regenerative approach capable of preserving tooth pulp vitality.

Minocycline Hydrochloride Controlled-release Microsphere Preparation Process Optimization Based on the Robust Design Method.

The objective of the present study is to establish a robust preparation method that could steadily produce minocycline hydrochloride (MCH) microspheres regardless of used polymer types. Taguchi's Robust Experimental Design methodology was employed to optimize the process parameters for MCH-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. In the experimental design, seven controllable factors, i.e., preparation method, pH of the aqueous phase, volume of the aqueous phase, volume of dichloromethane, rotation speed, temperature, and amount of polyvinyl alcohol, were considered for the optimization of process parameters. PLGA types with different lactide/glycolide ratios were considered the uncontrollable (noise) factor. Based on the L18 orthogonal array, 18 experimental runs were conducted for each type of PLGA. The encapsulation efficiency (EE) and in vitro release rate were evaluated for all the prepared formulations. Regardless of the PLGA type with different lactic/glycolic acid ratios, microspheres prepared via the solid-in-oil-in-water (S/O/W) method, showed a much higher EE and faster drug release than the microspheres prepared via the co-solvent method. Preparation methods, pH of the aqueous phase, and volume of the aqueous phase were the most influencing parameters on the EE. The confirmation experiment results indicated that the signal-to-noise ratio increased by 5.76 db from that of an initial condition. The release of minocycline was fastest with the PLGA (50:50) microspheres, followed by PLGA (75:25) and PLGA (85:15). Although the interaction between the selected factors in the evaluation was ignored, the orthogonal array design of the experiment based on Taguchi's robust experimental design methodology was sufficient to optimize the process parameters for the PLGA microspheres of MCH. The S/O/W was the main factor affecting the EE. Microspheres prepared via the S/O/W method exhibited a higher EE and faster drug release than the microspheres prepared via co-solvent method. The pH and volume of the aqueous phase were also effective parameters on the EE. A robust experimental design has been successfully applied to the optimization of the process parameters for microsphere preparation.

DoE approach for development of localized controlled release microspheres of Vancomycin for treatment of septic arthritis

BackgroundSeptic arthritis is a worse condition of RA that is associated with significant morbidity and mortality. Septic arthritis develops due to direct introduction or invasion of pathogens. The objective of the present study was to formulate Vancomycin hydrochloride-loaded microspheres (VMS) based on Box–Behnken design (BBD) and evaluate its efficacy against septic arthritis. The intraarticular administration of optimized Vancomycin hydrochloride-loaded microspheres (OVMS) can reduce dose size, dosing frequency and systemic exposure with local targeted delivery.ResultsOVMS was further characterized for its drug–polymer compatibility using differential scanning calorimetry and Fourier transmission infrared spectroscopy. In vitro antibacterial activity was determined using the cup–plate method and in vivo anti-arthritic efficacy was evaluated by gross examination of septic arthritis. DSC and FTIR studies exhibited no interaction or incompatibilities between the drug and polymer. SEM images revealed that OVMS were spherical. It followed the first-order release rate according to Fick's law. The micromeritic properties indicated good flow property of OVMS. The zone of inhibition by OVMS was 1.5 cm against S. aureus. In vivo antibacterial study revealed that OVMS was significant in reducing septic arthritis and bacterial load, i.e., 110.1 CFU/ml in comparison with the control group (850 CFU/ml).ConclusionsThus, OVMS may be used as an effective formulation for the treatment of septic arthritis as compared to marketed IV vancomycin injection after clinical studies.

MUCOADHESIVE MICROSPHERES OF QUINAPRIL HYDROCHLORIDE FOR THE MANAGEMENT OF HYPERTENSION VIA ORAL ROUTE: AN APPROACH

The objective of the present study is to create a new approach to design and evaluate mucoadhesive microspheres for oral controlled release. The quinapril hydrochloride microspheres with a coat consisting of alginate polymer i.e. sodium alginate in combination of mucoadhesive mineral origin chitin molecule polymer chitosan and galactomannan polymer i.e. guargum were prepared by an ionic gelation process. The microspheres were evaluated for morphological character, particle size, micromeritic properties, percentage entrapment efficiency, Swelling Index, in-vitro wash-off test, in-vitro release studies and in vivo mucoadhesion behavior in albino rabbits. The result of mucoadhesive microspheres were identified spherical and have free flowing properties. The percent of drug loading efficiency was 89.9 to 95.6%. The microspheres showed good mucoadhesive property during the in vitro wash-off test. The drug quinapril hydrochloride released from polymer matrix mucoadhesive system from these was slow and extended over 12 h duration on the composition of coat. Mucoadhesive microspheres provide the capability to adhere on the mucosal tissue of stomach. Quinapril Hydrochloriderelease mucoadhesive pulsatile multiunit dosage forms was found to be slow and extended period of time. The drug discharge ratio was dependent on the composition of polymer and stirring speed used during the formulation. The release of drug was prolonged through the matrix system produced after swelling of polymeric composition of coat within mucoadhesive polymers and sustained drug release up to 12 h duration. The result concluded that prepared mucoadhesive microspheres best suited for oral controlled release of quinapril hydrochloride for the management of hypertension via oral route.

Preparation and evaluation of microspheres with dual polymeric film to minimize burst effect of highly water soluble drug

Double-layered controlled release microspheres of venlafaxine were prepared using ethyl cellulose (EC) as a wall forming hydrophobic polymer. Usually, it is difficult to control initial sudden release of highly water-soluble drugs. In this regard, double-layered microparticles were prepared not only for controlling initial burst effect but also to sustain the release of venlafaxine for an extended period of time. Solvent evaporation technique based on O/O emulsion was applied to prepare modified release microparticles. To minimize initial burst effect, developed microparticles were again coated with same hydrophobic polymer. Percent recovery, drug loading efficiency and particle size were measured. FTIR, SEM and kinetic models were applied to characterize venlafaxine microspheres. Packing and flow properties of microparticles were satisfactory. FTIR spectra of EC, venlafaxine and venlafaxine loaded microspheres were recorded. SEM analysis showed the formation of spherical microspheres with slightly rough surface. Burst effect of venlafaxine was significantly retarded in double-layered microparticles. Drug release databased on highest values of correlation coefficient, was suitably explained by Higuchi kinetics and mechanism of release was Fickian diffusion. This study strongly suggests that double-layered microspheres can successfully be applied for controlling the dose dumping and sustaining the release of highly water-soluble drug for an extended period of time.

USING THE BOX–BEHNKEN EXPERIMENTAL DESIGN DEVELOPMENT OF GASTRORETENTIVE MUCOADHESIVE MICROSPHERES OF SIMVASTATIN BY SPRAY DRYING METHOD

Simvastatin is an antihyper-lipidemic drug which inhibits HMG-CoA reductase, interrupting cholesterol synthesis. It is poorly water soluble drug having very low bioavailability (5%). It is having better absorption in upper gastro intestinal tract. Due to lower bioavailability and short biological half-life simvastatin is prescribed 2-3 times a day which leads to lower patient compliance. The aim of the present work was to prepare controlled release microspheres which and retained in the gastric area by adhering to the mucosal membrane for longer period of time. It was a also proposed to design and optimize the formulation and process parameters for preparation of gastroretentive simvastatin microspheres using spray drying technique. The major problem associated with oral drug delivery is ineffective absorption and low bioavailability because drugs having narrow absorption window. Simvastatin microspheres was prepared using polymer HPMC K4M as carrier polymer and Eudragit RSPO were prepared using spray drying technique. The in vitro evaluation of mucoadhesive property of simvastatin microspheres was done on goat intestinal mucosa which showed strong mucoadhesion of 85% up to 6 hours. The in vitro drug release studies of microspheres were performed in 0.01 M sodium phosphate containing 0.5% SLS using syringe pump for 8 h.

A thermoresponsive hydrogel system for long-acting corticosteroid delivery into the paranasal sinuses

Delivering localized treatment to the paranasal sinuses for diseases such as chronic rhinosinusitis (CRS) is particularly challenging because of the small natural openings leading from the sinuses that can be further obstructed by presence of inflammation. As such, oral steroids, topical nasal sprays or irrigation, and surgery can be utilized to treat persistent sinonasal inflammation, but there exists a need for post-operative options for long-term steroid delivery to prevent disease recurrence. In the present study, a Thermogel, Extended-release Microsphere-based-delivery to the Paranasal Sinuses (TEMPS) is developed with the corticosteroid mometasone furoate. Specifically, the bioactive steroid is released for 4 weeks from poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly(N-isopropylacrylamide) (p-NIPAAm)-based hydrogel. The temperature-responsive system undergoes a reversible sol-gel transition at 34–35 °C such that it can be applied as a liquid at ambient temperature, conforming to the sinonasal epithelium as it gels. In a rabbit model of CRS, TEMPS was maintained in rabbit sinuses and effectively reduced sinonasal inflammation as characterized by micro-computed tomography and histopathology analysis. Ultimately, the combination of controlled release microspheres with a thermoresponsive hydrogel provides flexibility for encapsulating therapeutics in a reversible and conforming system for localized delivery to the sinuses.

VEGF-PLGA controlled-release microspheres enhanced angiogenesis in encephalomyosynangiosis-based chronic cerebral hypoperfusion

Treatments enhancing angiogenesis for chronic cerebral hypoperfusion (CCH) are still in the research stage. Although encephalomyosynangiosis (EMS) is a common indirect anastomosis for the treatment of CCH, the effectiveness to promote angiogenesis is not satisfactory. Vascular endothelial growth factors (VEGF) is a cytokine found to specifically act directly on vascular endothelial cells, promote neovascularization, and enhance capillary permeability. However, the short half life and unstable property of VEGF underlies the need to explore available delivery system. In this study, poly (lactide-co-glycolide) (PLGA) was used to prepare VEGF controlled-release microspheres. In vitro and in vivo analysis of release kinetics showed that the microspheres could release VEGF continuously within 30 days. Then, modified chronic cerebral hypoperfusion rat model was established by ligation of bilateral internal carotid artery and one vertebral artery. At 14 days after ischemia, the EMS and the VEGF microspheres injection were performed. At 30 days after the injection, the result of Morris water maze displayed that combinating VEGF microspheres and EMS significantly ameliorated cognitive deficit after ischemia. We observed that combinating VEGF microspheres and EMS could further significantly increase cerebral blood flow. We speculated that this enhancement of cerebral blood flow was attributed to more angiogenesis induced by combination of VEGF microspheres and EMS, which verified by more collateral circulation with cerebral angiography and higher expression of CD31 or α-SMA. Our study demonstrated that combinating VEGF-PLGA controlled-release microspheres could significantly promote angiogenesis in EMS-based CCH rats model, providing new ideas for clinical treatment of CCH.

Characterization of Controlled Release Microspheres Using FIB-SEM and Image-Based Release Prediction

For polymer-based controlled release drug products (e.g. microspheres and implants), active pharmaceutical ingredient distribution and microporosity inside the polymer matrix are critical for product performance, particularly drug release kinetics. Due to the decreasing domain size and increasing complexity of such products, conventional characterization and release test techniques are limited by their resolution and speed. In this study, samples of controlled release poly(lactic-co-glycolic acid) microspheres in the diameter range of 30-80μm are investigated with focused ion beam scanning electron microscope imaging at 20nm or higher resolution. Image data is quantified with artificial intelligence-based image analytics to provide size distributions of drug particles and pores within the microsphere sample. With an innovative image-based numerical simulation method, release profiles are predicted in a matter of days regardless of the designed release time. A mechanistic understanding on the impact of porosity to the interplays of drug, formulation, process, and dissolution was gained.

Synthesis and characterization of dopamine-modified Ca-alginate/poly(N-isopropylacrylamide) microspheres for water retention and multi-responsive controlled release of agrochemicals

The multi-responsive controlled-release system could enhance crop yield while improving utilization efficiency of agrochemicals, and minimize environmental pollution caused by agrochemicals overuse. This work reports a novel Ca-alginate/Poly(N-isopropylacrylamide)@polydopamine (Ca-alginate/PNIPAm@PDA) microsphere to control the agrochemicals release. Microsphere with a semi-interpenetrating network, which contained pH-sensitive Ca-alginate, temperature-sensitive poly(N-isopropylacrylamide) (PNIPAm), and sunlight-sensitive polydopamine (PDA), was characterized by thermogravimetric analysis, zeta potential, Fourier transform infrared spectroscopy, and scanning electron microscopy to prove the successful synthesis. Moreover, the comprehensive performances, including photothermal conversion, water absorbency, water retention, and controlled-release agrochemicals behaviors, were systematically investigated. The results indicated that the composite microsphere was a prosperous water and agrochemicals manager to effectively retain water and control the release of agrochemicals by external stimulation. Consequently, the Ca-alginate/PNIPAm@PDA microsphere with outstanding water-retention and controlled-release capacities is economical and eco-friendly and thus is promising for utilization as water and agrochemicals controlled-release carrier material in agriculture applications.

Fabrication and characterization of hexadecyl acrylate cross-linked phase change microspheres

Abstract Microspheres with phase change properties were fabricated by polymerization of hexadecyl acrylate (HA) and different cross-linking agents. The samples were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA). The results show that, the samples that added cross-linking agents have a smooth surface and the latent heat of them is different. The experiments show that all of the cross-linked copolymer shells can be made into temperature controlled release microspheres. These materials can be potentially applied in the field of thermal energy storage. β-tricalcium phosphate was encapsulated in microspheres to obtain one with a fast release effect. It will effectively promote bone conduction when these microspheres were implanted into a bone defect. This microsphere can be used for orthopedic implant or coating of instrument in the future.