Microsphere Loading Research Articles

Effects of HepaSphere microsphere encapsule epirubicin with a new loading method transarterial chemoembolization: in vitro and in vivo experiments

MethodsHS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed.ResultsIt was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 μm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%.ConclusionsThe size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.

Adhesive and Injectable Hydrogel Microspheres for Inner Ear Treatment (Small 36/2022)

Inner Ear Therapy In article number 2106591, Bin Ye, Wenguo Cui, Mingliang Xiang, and co-workers construct a mussel-inspired injectable hydrogel microsphere loading Ebselen liposomes that adheres to the cochlea round windows membrane (RWM). The positively charged primary amine groups through electrostatic interaction and the catechol groups through high-strength coordination bonds and hydrogen bonds adhere to the RWM. This adhesion can prolong the retention of the middle ear cavity for more than 7 days and helps with inner ear therapy.

Effect of Surface Interactions on Microsphere Loading in Dissolving Microneedle Patches.

Microneedle (MN) patches enable simple self-administration of drugs via the skin. In this study, we sought to deliver drug-loaded microspheres (MSs) using MN patches and found that the poly(lactic-co-glycolic acid) (PLGA) MSs failed to localize in the MN tips during fabrication, thereby decreasing their delivered dose and delivery efficiency into skin. We determined that surface interactions between the hydrophobic MSs and the poly(dimethylsiloxane) (PDMS) mold caused MSs to adhere to the mold surface during casting in aqueous formulations, with hydrophobic interactions largely responsible for adhesion. Further studies with polystyrene MSs that similarly carry a negative charge like the PLGA MSs demonstrated both repulsive electrostatic interactions as well as adhesive hydrophobic interactions. Reducing hydrophobic interactions by addition of a surfactant or modifying mold surface properties increased MS loading into MN tips and delivery into porcine skin ex vivo by 3-fold. We conclude that surface interactions affect the loading of hydrophobic MSs into MN patches during aqueous fabrication procedures and that their modulation with the surfactant can increase loading and delivery efficiency.

Developing Echogenic Materials as Catheters for Use with Ultrasound.

Patients with peripherally inserted central catheters (PICCs) are routinely discharged with the catheters in place. These patients experience complications due to undetected thrombosis or accidental dislodgement, with tracking through limited X-ray imaging. Developing catheters with the capability to be tracked without the need for X-ray imaging would greatly benefit these patients by decreasing patient stress, reducing time to diagnosis, and increasing nursing home capabilities. This study reports on the incorporation of echogenic microspheres into catheters to produce bulk echogenic effects for developments in the field of real-time ultrasound tracking of polymeric medical devices. The impact on elastic modulus, ultrasound contrast, and cytocompatibility of the polymer was analyzed when incorporating up to 10 wt % glass microspheres. Up to this loading level, the elastic modulus was found to remain constant. However, at 10 wt %, extrusion defects due to agglomeration, air bubbles, and shearing were numerous and deemed detrimental to ultrasound imaging. Successful, defect-free samples were produced with 5 wt % microsphere loading and when embedded in a soft tissue phantom revealed a significant increase in the signal-to-noise ratio as compared to the polymer alone. Preliminary results have shown a successful increase in polymer's echogenic properties, without undermining its mechanical and cytocompatibility properties.

Characterization of Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Ranibizumab.

PurposeTo characterize a biodegradable microsphere-hydrogel drug delivery system (DDS) for controlled and extended release of ranibizumab.MethodsThe degradable microsphere-hydrogel DDSs were fabricated by suspending ranibizumab-loaded or blank poly(lactic-co-glycolic acid) microspheres within a poly(ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) hydrogel. The thermal responsive behavior of various DDS formulations was characterized in terms of volume phase transition temperature (VPTT) and swelling ratios changes from 22°C to 42°C. The mechanical properties were characterized using rheological methods. Degradability of hydrogels were also examined via wet weight loss. Finally, Iodine-125 was used to radiolabel ranibizumab for characterization of encapsulation efficiency and in vitro release.ResultsAll DDS formulations investigated were injectable through a 28-gauge needle at room temperature. The VPTT increased with increase of cross-linker concentration. The swelling ratios decreased as temperature increased and were not influenced by presence of microspheres. Rheology data confirmed that increase of cross-linker concentration and microsphere loading made DDS stiffer. Increase of degradable cross-linker concentration facilitated hydrogel in vitro degradation. Controlled release of ranibizumab were achieved for investigated DDS formulations for 6 months; and increased degradable cross-linker concentration produced faster and more complete release.ConclusionsThe biodegradable DDSs are suitable for sustained release of ranibizumab. Considering ease of injection, degradability and release of ranibizumab, DDS with 3 mM cross-linker concentration and less than 20 mg/mL microsphere loadings is more favorable for future application.Translational RelevanceThe investigated DDS is promising for controlled and extended release of anti-VEGF therapeutics to achieve better treatment regimen in ocular neovascularizations.

Biological properties and enzymatic degradation studies of clindamycin-loaded PLA/HAp microspheres prepared from crocodile bones

Polylactic acid (PLA)/hydroxyapatite (HAp) biocomposite microspheres with a specific core–shell structure for application as drug carriers were synthesised using an ultrasound field. In addition, the loading efficiency of clindamycin phosphate increased when the HAp content was increased to 30%. The effect of HAp content on enzymatic degradation of PLA/HAp microspheres loaded with clindamycin phosphate was that the degradation rate increased with increasing HAp content. Apatite formed on the surfaces of the PLA and PLA/HAp microsphere loading of clindamycin phosphate showed Ca and P peaks in energy-dispersive X-ray spectroscopy (EDX) data. In addition, the PLA and PLA/HAp microspheres loaded with clindamycin phosphate did not show any cytotoxicity against the human lung fibroblast MRC-5.

Preparation, Characterization and Prophylactic Study of New Microsphere Containing Doxycycline against Diseases of Shrimp

Therapeutically and prophylactically using Microspheres containing doxycycline isolated from shell of shrimp. Low molecule weight poly lactic acid was prepared. In this study, Poly lactic acid (PLA)/ poly vinyl alcohol (PVA)/poly ethyleneglycol(PEG) loading doxycycline blend solutions was prepared. Also Poly lactic acid (PLA)-Tannin blend via solvent evaporation method was prepared. Microspheres of chitosan/gelatin microsphere loading doxycycline was prepared by emulsion crosslinking technique. Both microsphere and blends were characterized by Fourier transform infrared (FTIR) spectrophotometer. The FTIR spectra were shown distinguish bands. The in vitro release of doxcycline from its matrix at pH 7 was studied. The prophylactic against white spot (Ich) disease of shrimp (Macrobrachium nipponense) was studied. The results were shown increase of percentage of survival of shrimp in both microsphere and blend compared with control. The highly percentage of survival was shown in the microsphere compare with blends.&#x0D; Key words: Chitosan, Microsphere, Polymer blend, Shrimp, Prophylactic.&#x0D;

Pebax–polydopamine microsphere mixed‐matrix membranes for efficient CO2 separation

ABSTRACTNovel facilitated‐transport mixed‐matrix membrane (MMM) were prepared through the incorporation of polydopamine (PDA) microspheres into a poly(amide‐b‐ethylene oxide) (Pebax MH 1657) matrix to separate CO2–CH4 gas mixtures. The Pebax–PDA microsphere MMMs were characterized by Fourier transform infrared spectroscopy, scanning electron microcopy, X‐ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The PDA microspheres acted as an adhesive filler and generated strong interfacial interactions with the polymer matrix; this generated a polymer chain rigidification region near the polymer–filler interface. Polymer chain rigidification usually results in a larger resistance to the transport of gas with a larger molecular diameter and a higher CO2–CH4 selectivity. In addition, the surface of PDA microspheres contained larger numbers of amine, imine, and catechol groups; these were beneficial to the improvement of the CO2 separation performance. Compared with the pristine Pebax membrane, the MMM with a 5 wt % PDA microsphere loading displayed a higher gas permeability and selectivity; their CO2 permeability and CO2–CH4 selectivity were increased by 61 and 60%, respectively, and surpassed the 2008 Robeson upper bound line. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44564.

Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications.

Bio-degradable poly(lactide) (PLA)/poly(lactide-glycolide) (PLGA) and chitosan microspheres (or microcapsules) have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. By encapsulating protein/peptide drugs in the microspheres, the serum drug concentration can be maintained at a higher constant value for a prolonged time, or injection formulation can be changed to orally or mucosally administered formulation. PLA/PLGA and chitosan are most often used in injection formulation and oral formulation. However, in the preparation and applications of PLA/PLGA and chitosan microspheres containing protein/peptide drugs, the problems of broad size distribution and poor reproducibility of microspheres, and deactivation of protein during the preparation, storage and release, are still big challenges. In this article, the techniques for control of the diameter of microspheres and microcapsules will be introduced at first, then the strategies about how to maintain the bioactivity of protein drugs during preparation and drug release will be reviewed and developed in our research group. The membrane emulsification techniques including direct membrane emulsification and rapid membrane emulsification processes were developed to prepare uniform-sized microspheres, the diameter of microspheres can be controlled from submicron to 100μm by these two processes, and the reproducibility of products can be guaranteed. Furthermore, compared with conventional stirring method, the big advantages of membrane emulsification process were that the uniform microspheres with much higher encapsulation efficiency can be obtained, and the release behavior can be adjusted by selecting microsphere size. Mild membrane emulsification condition also can prevent the deactivation of proteins, which frequently occurred under high shear force in mechanical stirring, sonification, and homogenization methods. The strategies for maintaining the bioactivity of protein drug were developed, such as adding additives into protein solution, using solid drug powder instead of protein solution, and employing hydrophilic poly(lactide)-poly(ethylene glycol) (PELA) as a wall material for encapsulation in PLA/PLGA microspheres/microcapsules; developing step-wise crosslinking process, self-solidification process, and adsorbing protein drug into preformed chitosan microsphere with hollow-porous morphology for encapsulation in chitosan microsphere. As a result, animal test demonstrated that PELA microcapsules with uniform size and containing recombinant human growth hormone (rhGH) can maintain higher blood drug concentration for 2months, and increased animal weight more apparently only by single dose, compared with PLA and PLGA microcapsules; hollow-porous chitosan microsphere loading insulin decreased blood glucose level largely when it was used as a carrier for oral administration.

Mathematical modelling of glycosaminoglycan production by stem cell aggregates incorporated with growth factor-releasing polymer microspheres.

Systems composed of high density cells incorporated with growth factor-releasing polymer microspheres have recently been shown to promote chondrogenic differentiation and cartilage formation. Within these systems, the effects of spatial and temporal patterning of growth factor release on hyaline cartilage-specific extracellular matrix production have been examined. However, at present, it is unclear which microsphere densities and growth factor delivery profiles are optimal for inducing human mesenchymal stem cell differentiation and glycosaminoglycan production. A mathematical model to describe glycosaminoglycan production as a function of initial microsphere loading and microsphere degradation rate over a period of 3 weeks is presented. Based on predictions generated by this model, it may be feasible to design a bioactive microsphere system with specific spatiotemporal growth factor presentation characteristics to promote glycosaminoglycan production at controllable rates. Copyright © 2014 John Wiley & Sons, Ltd.

Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration

Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO2) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer's molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO2 scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO2 scaffold for future vascularization of the scaffold. The ZrO2 composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration.

Effect of Dexamethasone-Loaded Poly(Lactic-Co-Glycolic Acid) Microsphere/Poly(Vinyl Alcohol) Hydrogel Composite Coatings on the Basic Characteristics of Implantable Glucose Sensors

Hydrogels alone and in combination with microsphere drug delivery systems are being considered as biocompatible coatings for implantable glucose biosensors to prevent/minimize the foreign body response. Previously, our group has demonstrated that continuous release of dexamethasone from poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composites can successfully prevent foreign body response at the implantation site. The objective of this study was to investigate the effect of this composite coating on sensor functionality. The PLGA microsphere/PVA hydrogel coatings were prepared and applied to glucose biosensors. The swelling properties of the composite coatings and their diffusivity to glucose were evaluated as a function of microsphere loading. Sensor linearity, response time, and sensitivity were also evaluated as a function of coating composition. The PLGA microsphere/PVA hydrogel composite coating did not compromise sensor linearity (sensors were linear up to 30 mM), which is well beyond the physiological glucose range (2 to 22 mM). The sensor response time did increase in the presence of the coating (from 10 to 19 s); however, this response time was still less than the average reported values. Although the sensitivity of the sensors decreased from 73 to 62 nA/mM glucose when the PLGA microsphere loading in the PVA hydrogel changed from 0 to 100 mg/ml, this reduced sensitivity is acceptable for sensor functionality. The changes in sensor response time and sensitivity were due to changes in glucose permeability as a result of the coatings. The embedded PLGA microspheres reduced the fraction of bulk water present in the hydrogel matrix and consequently reduced glucose diffusion. This study demonstrates that the PLGA microsphere/PVA hydrogel composite coatings allow sufficient glucose diffusion and sensor functionality and therefore may be utilized as a smart coating for implantable glucose biosensors to enhance their in vivo functionality.

Preparation and characterization of chitosan microsphere loading bovine serum albumin.

To optimize the preparation process of chitosan microspheres and study its loading capacity, chitosan microsphere was prepared by crosslinking with glutaraldehyde, and bovine serum albumin (BSA) was absorbed onto chitosan microsphere. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FITR), TA instruments and zeta potentiometer analyzer were used to characterize the parameters with respect to size, thermal characters, morphology, and zeta potential of the microspheres. The loading capability and in vitro release tests were carried out. The results showed that chitosan microsphere with particle size less than 10 μm and positively charged (+25.97±0.56 mV) can be obtained under the aldehyde group to amino group ratio at 1:1. A loading capacity of BSA at 28.63±0.15 g/100 g with corresponding loading efficiency at 72.01±1.44% was obtained for chitosan microsphere. In vitro test revealed a burst release followed by sustained-release profile.

Hydrogel Matrix Entrapping PLGA-Paclitaxel Microspheres: Drug Delivery with Near Zero-Order Release and Implantability Advantages for Malignant Brain Tumour Chemotherapy

To develop paclitaxel-delivering PLGA microspheres entrapped in a gel matrix with sustained drug release properties and implantability advantages for local glioma chemotherapy. Paclitaxel-loaded PLGA microspheres were fabricated using electrohydrodynamic atomization and entrapped by electrospray and gelation. The physicochemical characterizations were performed using scanning electron microscopy and differential scanning calorimetry. The influence of various parameters on the disintegration time was investigated. In vitro release of paclitaxel was quantified using high performance liquid chromatography. Cytotoxicity of the formulations was assessed by the quantification of IC(50) and caspase-3 activity against C6 glioma cells in vitro. The formulations were tested against a subcutaneous C6 glioma tumour in mice. Highly monodisperse gel beads containing a uniform microsphere distribution were obtained. Gelation using Ca(2+) ions ensured entrapment of microspheres with high loading efficiency. With an increase in the gelation time, gelling bath concentration and decrease in microsphere loading, it was more difficult to disintegrate the beads and release the microspheres. The formulations demonstrated sustained drug release for more than 60 days at a near-constant rate and a low initial burst. Cell culture studies proved the cytotoxicity against C6 glioma and improved performance in comparison to Taxol. The formulations could reduce subcutaneous tumour volume to a greater extent compared to Taxol and the control. Paclitaxel-loaded PLGA microspheres entrapped in an alginate gel matrix could be potential local chemotherapy implants to treat malignant glioma with critical advantages of implantability and sustained drug release with low initial burst.

Magnetic microsphere-based mixers for microdroplets

While droplet-based microfluidic systems have several advantages over traditional flow-through devices, achieving adequate mixing between reagents inside droplet-based reactors remains challenging. We describe an active mixing approach based on the magnetic stirring of self-assembled chains of magnetic microspheres within the droplet as these stirrers experience a rotating magnetic field. We measure the mixing of a water-soluble dye in the droplet in terms of a dimensional mixing parameter as the field-rpm, fluid viscosity, and microsphere loading are parametrically varied. These show that the mixing rate has a maximum value at a critical Mason number that depends upon the operating conditions.

Composite Tectocapsules Containing Porous Polymer Microspheres as Release Gates

Porous and amphiphilic polymer microspheres were incorporated into polyurea capsules in order to control the release of the core solvents independently of wall formation. While nonpolar poly(divinylbenzene-55) microspheres were simply encapsulated along with the xylene core solvent, the amphiphilic poly(divinylbenzene-55-alt-maleic anhydride) microspheres, as well as maleic acid functionalized poly(divinylbenzene-55) microspheres, became embedded at the polyurea−water interface. Release of xylene from these microcapsules into air was monitored at room temperature and 50 °C. Release profiles change significantly upon addition of amphiphilic porous microspheres, with the release rates scaling with microsphere loading. Scanning transmission X-ray spectromicroscopy (STXM) indicates that the polyurea is largely excluded from the pores of the microspheres.

Relative dielectric permittivity of calcium aluminate cement-glass microsphere composites

Calcium aluminate cement (SECAR TM 80) was loaded with 0, 27.5, 40, 50, 60 and 70 vol% hollow glass microspheres and processed macro-defect free by high shear mixing with polyvinyl alcohol as a rheological aid. Discs were formed by die-pressing and dielectric measurements obtained from 100 Hz to 2 MHz. Relative dielectric permittivity was lowered for all microsphere loadings and was lowest at 40 vol%, corresponding to an effective porosity of 21.7%. A direct correlation was found to exist between microsphere loading (effective porosity) and the relative dielectric permittivity. Volume loadings of 27.5 and 40% microspheres resulted in the largest number of unbroken microspheres after processing. When compared with four ideal dielectric mixing models, the cement-microsphere composites were found to correlate best with Maxwell and Lichtenecker mixing. Dissipation factor was lower over the measured frequency range for all microsphere loadings. No correlation was found to exist between effective porosity and dissipation factor. Dielectric losses at low frequencies can be attributed to unbound water and polyvinyl alcohol.