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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.
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.
Since their discovery in 1965, by Alec D. Bangham, liposomes have been recognised as the drug delivery vehicle of choice. Their biocompatibility results in minimal adverse reactions. Their amphiphilic structure allows encapsulation of both hydrophilic and hydrophobic active pharmaceutical ingredients (APIs). More recently the liposome’s analogous cousin, the lipid nanoparticle, has gained prominence because of its ability to deliver therapeutic payloads, including DNA and mRNA for vaccines. They can both deliver their payload very precisely through treating their surface with proteins allowing highly specific binding to a target cell type. This paper describes the advantages, over the most common commercial processes, that Micropore's membrane emulsification technology has in Liposomes and Lipid nanoparticle production.
Commercialisation of sustained release formulations began in the 1970s with PLA & PGA used for surgical implants and sutures. PLGA (Poly (lactic acid-co-glycolic acid)) quickly emerged as the most important biocompatible, non-toxic polymer with numerous applications in drug delivery, tissue engineering, medical and surgical devices. PLGA is approved worldwide for several therapeutic applications because of its biodegradability, biocompatibility and sustained-release properties. Despite this longevity, PLGA is not easy to formulate into sustained release drug products with the result that inventor drug products and generic versions remain scarce with only 20 drugs approved in 30+ years. Aseptic membrane emulsification devices can now be used to form PLGA microspheres from lab scale to full scale manufacturing using the well-proven solvent evaporation method of production.
Hydrogels consist of three-dimensional, hydrophilic, polymeric networks capable of holding large quantities of solvated hydrophilic drugs. Since the early 1960s they have been considered for controlled release of trapped drugs, both small molecule and macromolecular drugs, through slow diffusion. They possess tuneable properties and the capability to protect labile drugs from degradation controlling their release. Their resemblance to living tissue opens up many opportunities for biomedical applications. Currently, hydrogels are used for manufacturing contact lenses, hygiene products, wound dressings, tissue engineering scaffolds and drug delivery systems.
Membrane emulsification sidesteps the challenges of creating hydrogels by forming droplets directly as a w/o emulsion with precise size control forming perfectly spherical droplets in sizes less than 50µm.
Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
The term coacervation derives from the Latin verb “coacervare”, meaning “to crowd together”. The technique of coacervation was first characterised by Bungenberg de Jong in 1931, although the earliest reports of this technique go back to Tiebackx in 1911. Over the last 2-3 decades complex coacervation has been deployed in industries as diverse as food, cosmetics, agriculture and functional materials, as well as, more recently, generating an increasing interest in the pharmaceutical industry as a drug delivery mechanism. This White Paper focuses on drug delivery using complex coacervation. Achieving an accurate target capsule size in an industrial setting can be a challenge While the homogeniser is running, samples are taken and sized via electrozone sensing (Coulter principle) or laser diffraction. These techniques take time to run, and in the meantime the homogeniser continues to reduce the size of the emulsion droplets in the batch. This makes accurate sizing unpredictable.A preferred approach is a system where the desired size characteristics can be defined in advance and the emulsion produced in a single pass. Membrane emulsification makes this possible, by injecting the internal phase through the membrane pores and, by applying a known shear force, droplet sizes can be controlled precisely.
Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
Mesoporous silica particles (MSP) have gained wide popularity over recent years. Their advantages of uniform and tunable pore size, easy independent functionalization of the surface, internal and external pores and the gating mechanism of the pore opening make it a distinctive drug carrier. The unique feature of MSPs which makes them a widely exploited carrier for drug delivery is its high loading capacity due to the large pore volume and surface engineering properties both on the external and internal surface for better drug targeting. These versatile carriers can be used for loading a variety of cargos ranging from drugs to macromolecules such as proteins, DNA and RNA.
Through an improved, continuous, scalable sol-gel process both micro- and mesoporous near-monodispersed spherical particles can be produced in large continuous volumes using aseptic membrane emulsification devices with a range of internal pores between 1 and 12nm and an average surface area between 300 and 750 m2g-1.
Dave Palmer, Alex Kerr, Sam Trotter & Dai Hayward
The ability to deliver a drug to a patient in a safe, efficacious and cost-effective manner most commonly depends on the physicochemical properties of the active pharmaceutical ingredient (API) in the solid state. In this context, crystallisation is of critical importance in pharmaceutical industry as it defines physical and powder properties of crystalline APIs. Detailed knowledge of the various aspects of crystallisation process, and in particular, an understanding of the relationships between crystallisation, solid-state form and properties is required to deliver the desired therapeutic effect and to avoid undesirable effects.
Membrane crystallisation is a relatively new technique based on the use of a porous material as a semi-permeable barrier between two phases. The membrane can be used to create supersaturation by solvent evaporation, antisolvent or reactant addition, and mixing with a colder solvent . The ﬁrst membrane crystallisation process dates back to 1917 but recently, membranes have been used to crystallize proteins and macromolecules. The presence of a membrane adds a supplementary resistance to mass transfer, but it also offers additional control over nucleation kinetics.
Laura Carballido, Miriam Dabrowski, Friederike Dehli, Lukas Koch, Cosima Stubenrauch*
Institute of Physical Chemistry
Pfaffenwaldring 55, 70569 Stuttgart, Germany
*firstname.lastname@example.org, 0049 711 685-64470
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.
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.
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.
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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