Double-emulsion solvent-evaporation

The encapsulation of bioactive agents, such as proteins or peptides, presents a special problem due to the delicacy of their structural conformation. Their biological activity may be irreversibly disturbed even by small changes of pH, temperature, or ionic concentration [192,200]. Spray-drying and double emulsion solvent evaporation techniques (w/o/w) have been suggested for the incorporation of proteins with retention of their bioactivity [99,192,202,198]. 

When formulating lipophilic materials, techniques often involve the use of organic solvents, interfaces with aqueous solutions, and high-shear forces [6], One of the most often used techniques to encapsulate proteins is the water/oil/water (w/o/w) double-emulsion solvent evaporation technique, in which an aqueous protein solution is emulsified into an organic solution of the matrix material. This primary emulsion is added to an outer aqueous phase in which particles start to harden as the organic solvent evaporates. Alternatively, the solid protein can be added directly to the organic solution in a solid/oil/water (s/o/w) emulsion method [23],... 

FIGURE 47.4 Schematic procedure of double emulsion solvent evaporation method. 

Synthesis of polymer microspheres in the presence of magnetic nanoparticles, such as suspension polymerization or its modified versions, dispersion polymerization, surface-initiated radical polymerization, acid-catalyzed condensation polymerization, emulsion polymerization, mini-/microemulsion polymerization, in situ oxidative polymerization, inverse emulsion cross-linking, emulsion/double emulsion-solvent evaporation, and supercritical fluid extraction of o/w miniemulsion... 

Microspheres prepared by spray drying maintain their spherical geometry with a narrow size distribution with a mean diameter of 2-5 pm. Calceti et al. used suspension solvent evaporation, double emulsion-solvent evaporation, and suspension/double emulsion-solvent evaporation for the preparation of insulin-loaded polyphosphazene microspheres [80], These preparation procedures produced spherical microparticles with a porous surface and a honeycomb internal structure (Figure 11.11). 

FIGURE 11.11 Scanning electron microscopy of intact (a) and (b) fractured microspheres obtained by double emulsion-solvent evaporation using 20% insulin/polymer. Reprinted from Ref. [80] with permission from Elsevier. 

B. Double-emulsion-Solvent-evaporation Techniques for Preparation of Microspheres... 

It is known that the preparation of mierospheres by using 0/W emulsions is not an effieient method for die entrapment of water-soluble drugs as the eompounds rapidly dissolve in the aqueous eontinuous phase and are lost It has been widely aeeepted that the problem of inefficient eneapsulation of water-soluble dmgs ean be overcome by using the double-emulsion solvent-evaporation technique. Water-insoluble drugs are usually satisfactorily encapsulated by the 0/W emulsion teehnique (64, 65). 

The double-emulsion-solvent-evaporation technique is commonly used to prepare biodegradable hydro-phobic microspheres containing hydrophilic Pharmaceuticals, proteins, and polypeptides for sustained-release applications (66,70-78). In most cases the microspheres are in the range size 10-100 pm. However, recently, Blaneo-Prieto et al. (71) managed to reduce the microcapsule sizes to less than 5 pm. 

Water-soluble therapeutic proteins and peptides can be delivered using porous nanospheres or nanocapsules formed by a double emulsion solvent evaporation procedure. A concern with the delivery of proteins by nanoparticles is the loss of protein activity before its release. Desai et al. showed about 30% of tetanus toxoid activity was lost due after encapsulation and release from nanoparticles (Desai et al. 1996). Protein may be inactivated due to denaturation based on exposure to organic solvents and adsorption onto the oil-water interface during fabrication (van de Weert et al. 2000 Lu et al. 2000). A strategy for reducing adsorption of the therapeutic protein is the incorporation of human or bovine semm albumin in the aqueous phase, which restricts the access of the therapeutic protein to the phase interface (Kim and Park 1999). Another proposed cause of protein inactivation is decreased local pH experienced by the encapsulated protein due to acidic degradation byproducts. This can be addressed by including an alkaline buffer into the aqueous phase (Zhu et al. 2000). 

N. Zydowicz, E. Nzimba-Ganyanad, N. Zydowicz, PMMA microcapsules containing water-soluble dyes obtained by double emulsion/solvent evaporation technique, Polym. Bull. 2002, 47,457-463. 

To improve the oral bioavailability of calcitonin, Garcia-Fuentes et al. used tripalmitate nanoparticles coated with chi-tosan or polyethylene glycol. The nanoparticles were prepared by a double emulsion solvent evaporation method that was adapted due to its high efficiency for the encapsulation of peptides. The nanoparticles were stabilized with soybean lecithin and the surface coating was done by incubation of the prepared lipid nanoparticles in a chitosan/poloxamer solution or by initial addition of PEG-stearate to the organic phase. Excess stabilizers were removed by centrifugation. Whereas... 

The feasibility of using biodegradable poly(D,L-lactide-co-glycolide) microspheres produced by double emulsion solvent evaporation as an oral delivery system for bee venom phospholipase A2 was evaluated. It was found that the microspheres displayed optimal particle size for Peyer s patches uptake and that the integrity of the entrapped bee venom phospholipase A2 retained its specific IgE binding capacity, indicating the suitability of the microspheres as a potential delivery system for this application. 8 refs. 

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