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Scientific Papers

Welcome to our library of scientific papers relating to the science of membrane emulsification and encapsulation. Use our website site search tool to help locate papers relating to a specific research aspects.

Synthesis and Fabrication of Surface-Active Microparticles Using a Membrane Emulsion Technique and Conjugation of Model Protein via Strain-Promoted Azide–Alkyne Click Chemistry in Physiological Conditions

Grace Walden, Xin Liao, Graham Riley, Simon Donell, Michael J. Raxworthy, and Aram Saeed

The rapid surface immobilization of protein on monodispersed polyester microcarriers is reported. A model protein, functionalized with a dibenzocyclooctyne core, immobilizes on the surface of azide-terminal polycaprolactone microcarriers within 10 min compared to 12 h for other conjugation techniques, and it is conducted in physiological conditions and in the absence of coupling reagents.

Monodisperse Liquid Foams via Membrane Foaming

Laura Carballido, Miriam Dabrowski, Friederike Dehli, Lukas Koch, Cosima Stubenrauch*
Institute of Physical Chemistry
Pfaffenwaldring 55, 70569 Stuttgart, Germany
*cosima.stubenrauch@ipc.uni-stuttgart.de, 0049 711 685-64470​

Hypothesis
It is possible to generate fairly monodisperse liquid foams by a dispersion cell, which was originally designed for the generation of fairly monodisperse emulsions. If this is the case, scaling-up the production of monodisperse liquid and solid foams will be no longer a problem.

Experiments
We used the dispersion cell - a batch process - and examined the influence of stirrer speed, membrane pore diameter and injection rate on the structure of the resulting liquid foams. We used an aqueous surfactant solution as scouting system. Once the experimental conditions were known we generated gelatin-based liquid foams and methacrylate-based foamed emulsions.

Findings
We found that (a) the bubble size of the generated liquid foams can be adjusted by varying the membrane pore diameter, (b) no stirrer should be used to obtain monodisperse foams, and (c) the bubble size is not influenced by the air injection rate. Since (i) the output for all investigated systems is up to two orders of magnitude larger compared to microfluidics and (ii) the membrane technology can very easily be scaled-up if run in a continuous process, the use of membrane foaming is expected to be heavily used for the generation of monodisperse liquid and solid foams, respectively.

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

Karina C. Scheiner,† Roel F. Maas-Bakker,† Thanh T. Nguyen,‡ Ana M. Duarte,‡ Gert Hendriks,‡
Lídia Sequeira,‡ Garry P. Duffy,§ Rob Steendam,‡ Wim E. Hennink,† and Robbert J. Kok*,†
†Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG
Utrecht, The Netherlands
‡InnoCore Pharmaceuticals B.V., L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands
§Discipline of Anatomy, School of Medicine, National University of Ireland Galway, University Road, H91 TK33 Galway, Ireland

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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