Computer Modeling Assisted Design of Monodisperse PLGA Microspheres with Controlled Porosity Affords Zero Order Release of an Encapsulated Macromolecule for 3 Months

Kazazi-Hyseni, Filis; Landín, Mariana; Lathuile, Audrey; Veldhuis, Gert; Rahimian, Sima; Hennink, Wim E.; Kok, Robbert J.; Nostrum, Cornelus F. van

doi:10.1007/s11095-014-1381-8

Cited by 29 publications

(20 citation statements)

References 57 publications

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“…23,36 In order to obtain tailorable release of biopharmaceutical protein drugs, Kazazi-Hyseni et al prepared PLGA microspheres with differences in porosity by varying formulation parameters such as polymer concentration and oil/water ratios in a membrane emulsification process. 37 An alternative approach for tailoring the release of pharmaceutical proteins from polymeric microspheres is the use of phase-separated multiblock copolymers. 38,39 SynBioSys ® multiblock copolymers composed of amorphous poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) blocks and semicrystalline poly( l -lactic acid) (PLLA) blocks (as shown in Figure 1) are more hydrophilic than for example PLGA, due to the presence of PEG.…”

Section: Introductionmentioning

confidence: 99%

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres

Scheiner

Maas-Bakker

Nguyễn³

et al. 2019

ACS Omega

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Vascular endothelial growth factor (VEGF) is the major regulating factor for the formation of new blood vessels, also known as angiogenesis. VEGF is often incorporated in synthetic scaffolds to promote vascularization and to enhance the survival of cells that have been seeded in these devices. Such applications require sustained local delivery of VEGF of around 4 weeks for stable blood vessel formation. Most delivery systems for VEGF only provide short-term release for a couple of days, followed by a release phase with very low VEGF release. We now have developed VEGF-loaded polymeric microspheres that provide sustained release of bioactive VEGF for 4 weeks. Blends of two swellable poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone)- b -poly( l -lactide) ([PCL–PEG–PCL]- b -[PLLA])-based multiblock copolymers with different PEG content and PEG molecular weight were used to prepare the microspheres. Loading of the microspheres was established by a solvent evaporation-based membrane emulsification method. The resulting VEGF-loaded microspheres had average sizes of 40–50 μm and a narrow size distribution. Optimized formulations of a 50:50 blend of the two multiblock copolymers had an average VEGF loading of 0.79 ± 0.09%, representing a high average VEGF loading efficiency of 78 ± 16%. These microspheres released VEGF continuously over 4 weeks in phosphate-buffered saline pH 7.4 at 37 °C. This release profile was preserved after repeated and long-term storage at −20 °C for up to 9 months, thereby demonstrating excellent storage stability. VEGF release was governed by diffusion through the water-filled polymer matrix, depending on PEG molecular weight and PEG content of the polymers. The bioactivity of the released VEGF was retained within the experimental error in the 4-week release window, as demonstrated using a human umbilical vein endothelial cells proliferation assay. Thus, the microspheres prepared in this study are suitable for embedment in polymeric scaffolds with the aim of promoting their functional vascularization.

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Section: Introductionmentioning

confidence: 99%

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres

Scheiner

Maas-Bakker

Nguyễn³

et al. 2019

ACS Omega

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“…Due to the complexity of the interpretation of ANNs models, they are often combined with other Artificial Intelligence technologies such as fuzzy logic, giving hybrid systems [37,38]. The neurofuzzy logic technology used in this study combines the adaptive learning capabilities from ANNs and the ability to generalize rules of fuzzy.…”

Section: Introductionmentioning

confidence: 99%

Two-component thermosensitive hydrogels: Phase separation affecting rheological behavior

Abbadessa

Landín

Blenke

et al. 2017

European Polymer Journal

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Please cite this article as: Abbadessa, A., Landín, M., Oude Blenke, E., Hennink, W.E., Vermonden, T., Twocomponent thermosensitive hydrogels: Phase separation affecting rheological behavior, European Polymer Journal (2017), doi: http://dx. AbstractExtracellular matrices are mainly composed of a mixture of different biopolymers and therefore the use of two or more building blocks for the development of tissue-mimicking hydrogels is nowadays an attractive strategy in tissue-engineering. Multi-component hydrogel systems may undergo phase separation, which in turn can lead to new, unexpected material properties. The aim of this study was to understand the role of phase separation on the mechanical properties and 3D printability of hydrogels composed of triblock copolymers of polyethylene glycol (PEG) and methacrylated poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate) (pHPMAlac) blended with methacrylated hyaluronic acid (HAMA). To this end, hydrogels composed of different concentrations of PEG/pHPMAlac and HAMA, were analyzed for phase behavior and rheologicalproperties. Subsequently, phase separation and rheological behavior as function of the two polymer concentrations were mathematically processed to generate a predictive model. Results showed that PEG/pHPMAlac/HAMA hydrogels were characterized by hydrophilic, HAMA-richer internal domains dispersed in a more hydrophobic continuous phase, composed of PEG/pHPMAlac, and that the volume fraction of the dispersed phase increased by increasing HAMA concentration.Storage modulus, yield stress and viscosity increased with increasing HAMA concentration for low/medium HAMA contents (• 0.75% w/w), while a further increase of HAMA resulted in a 0.75% w/w), while a further increase of HAMA resulted in a decrease of the mentioned properties. On the other hand, by increasing the concentration of PEG/pHPMAlac these rheological properties were enhanced. The generated models showed a good fitting with experimental data, and were used to identify an exemplary 3D printability window for PEG/pHPMAlac/HAMA hydrogels, which was verified by rheological characterization and preparation of 3D printed scaffolds. In conclusion, a clear relationship between phase separation and rheological behavior in these two-component hydrogels can be described by complex functions of the two polymer concentrations. The predictive model generated in this study can be used as a valid tool for the identification of hydrogel compositions with desired, selected characteristics.3 Keywords: Thermosensitive polymers, hyaluronic acid, rheological properties, confocal laser scanning microscopy, neurofuzzy logic, 3D bioprinting. Highlights-Polymer ratios determine extent of phase separation in PEG/pHPMAlac/HAMA hydrogels.-Phase separation leads to hydrophilic domains dispersed in a more hydrophobic phase.-Phase separation affects rheological properties in a controllable fashion.-Mathematical models enabled a priori identification of hydrogels with desired properties.-Hydrogel 3D printing was achieved with a f...

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“…The particle sizes and size distributions of the microspheres were tested by Mastersizer laser diffraction (Malvern, UK). The size uniformity is expressed as the Span value, which was calculated as follows (Hu et al., 2012; Kazazi-Hyseni et al., 2014): where D v , 90%, D v , 50% and D v , 10% are the volume size diameters of the particles at 90%, 50% and 10% of the cumulative volume, respectively. The volume distributions are the default choice for many ensemble light scattering techniques including laser diffraction (Lai et al., 2014).…”

Section: Methodsmentioning

confidence: 99%

Uniform-sized insulin-loaded PLGA microspheres for improved early-stage peri-implant bone regeneration

Wang

Huan

et al. 2019

Drug Delivery

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Poor initial stability at the first four weeks after surgery is becoming the major causes for metal implant failure. Previous attempts neglected the control release of insulin for the bone regeneration among nondiabetic subjects. The major reason may lie in the adverse effects, such as attenuated bone formation, hypoglycemia or hyperinsulinemia, that caused by the excessive insulin. Thus, spatiotemporal release of insulin may serve as the promising strategy. To address this, through solvent extraction (EMS), solvent evaporation (SMS) and cosolvent methods (CMS), we prepared three types of PLGA microspheres with various internal structures, but similar size distribution. The effects of the preparation methods on the properties of the microspheres, such as their release behavior, degradation of molecular weight, and structural evolution, were investigated. Human bone marrow mesenchymal stromal cells (BMSCs) and rabbit implant models were used to test the bioactivity of the microspheres in vitro and in vivo, respectively. The result demonstrated that these three preparation methods did not influence the polymer degradation but instead affected the internal structural evolution, which plays a crucial role in the release behavior, osteogenesis and peri-implant bone regeneration. Compared with EMS and CMS microspheres, SMS microspheres exhibited a relatively steady release rate in the first four weeks, which evidently stimulated the osteogenic differentiation of the stem cells and peri-implant bone regeneration. Meanwhile, SMS microspheres significantly enhanced the stability of the implant at Week 4, which is promising to reduce early failure rate of the implant without inducing adverse effects on the serum biochemical indices.

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Computer Modeling Assisted Design of Monodisperse PLGA Microspheres with Controlled Porosity Affords Zero Order Release of an Encapsulated Macromolecule for 3 Months

Abstract: By fine-tuning the porosity, the release profile of PLGA microspheres for macromolecules can be predicted and changed from a three-phasic to a continuous release.

Cited by 29 publications

References 57 publications

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres

Two-component thermosensitive hydrogels: Phase separation affecting rheological behavior

Uniform-sized insulin-loaded PLGA microspheres for improved early-stage peri-implant bone regeneration

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