Nanocapsules solvent evaporation

Related to the generation of nanocapsules discussed above, is the appearance of rings or particles with single holes in hybrid system consisting of hydrophobic iron oxide, organic solvent, and polymer, probably in combination with KPS as initiator (see anchoring effect, Sect. 3.2). The emergence of these non-equilibrium structures is attributed to a delicate interplay of phase separation, viscosity, and solvent evaporation [191,192]. 

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). 

Nanoparticles consisting of different molecular weight PS-6-PMMA copolymers and nanocapsules made of the same copolymers, but additionally with hexadecane as liquid core material, were prepared by using a combined miniemulsion and solvent evaporation technique [220]. The morphology of block copolymer assemblies was investigated in dependence of the nanoconfinement. We introduced two nanoconfinement parameters the diameter D of the droplet throughout the synthesis and the shell thickness S of the nanocapsules with a liquid as core. D was controlled by varying the concentration of the surfactant in the miniemulsion, while 5 was controlled by the ratio of hexadecane to copolymer. 

The examples show the influence of the confinement on polymers. Nanoparticles and nanocapsules of PS-6-PMMA with different molecular weights were prepared. Their morphology could be precisely tuned by changing the amount of surfactant and hexadecane in double confinement. Also, the wall thickness of the capsules could be controlled by the amount of hexadecane employed during formation using a miniemulsion process with subsequent solvent evaporation. 

Finally the solvent evaporation process, that is generally the last step of the synthesis process, must be considered as it can cause an increase in the final particle size if the evaporation is carried out in a rotating evaporator imder moderate vacuum, a very limited variation is observed for both PCL and PEGylated copolymer, both in nanosphere and nanocapsule form, as shown in Figure 9.14 (compare also Figure 9.21 in Section 9.3 for an example with non-quenched particles) [72, 106 (supp. info.), 107]. In the case of loaded particles, different behaviors can be obtained in the case of PEGylated... 

Figure 9.14 Influence of solvent evaporation process on flnal particle size for PCL = 14,000) and PEGylated copolymer (initial concentration 6 mg/mL in acetone) both nanopheres of pure polymer and nanocapsules containing Miglyol are shown. Nanoparticles size measured after synthesis and quench in CIJM-dl (open symbols) and after solvent evaporator in a rotating evaporator (filled symbols) PCL...

Recent Advances in the Emulsion Solvent Evaporation Technique for the Preparation of Nanoparticles and Nanocapsules... 

Abstract The emulsion solvent evaporation technique is a method for preparing nanoparticles and nanocapsules that are particularly adapted for applications requiring materials with high purity and low toxicity, such as for biomedicine or electronics. We discuss here new important advances concerning the elucidation of the mechanism of nanoparticle formation, and the synthesis of nanoparticles with new structures or from new polymers. 

Fig. 2 Scheme showing the versatility of the emulsion-solvent evaporation technique for the preparation of nanocapsules. Polymers with completely different properties could be used to build the shell (left) while monomers for self-healing reactions based on various types of polymerization could be encapsulated as liquid core (right). PLLA poly(L-lactide), PVF poly(vinyl framal), PPO poly(phenylene oxide), PMMA poly(methyl methacrylate), PVCi poly(vinyl cinnamate), PVAc poly(vinyl acetate), OMCTS octamethylcyclotetrasiloxane, PDMS-DE polydimethylsiloxane diepoxy terminated [31]... 

Because the emulsion-solvent evaporation is versatile, new nanoparticles structures and nanoparticles from new materials are expected to be reported. Open questions such as how to create very monodisperse nanoparticles via this technique and the influence of the molecular state of the polymer on the nanoparticle and nanocapsule properties such as permeability are expected to be answered in the foreseeable future, helping to create more functional and useful materials. 

Nanocapsules act like a reservoir, which are called vesicular systems. They carry the active substance entrapped in the solid polymeric membrane or on their surfaces. The cavily inside contains either oil or water. A schematic diagram of Polymer Nanocapsules is shown in Fig. 9.2 [5], There are different methods that are used nowadays to prepare polymeric nanoparticles, such as nanoprecipitation (also termed as the solvent diffusion and solvent displacement method), solvent evaporation, dialysis, microemulsion, surfactant-free emulsion, salling-out, supercritical fluid technology, and interfacial polymerization [2]. Among these methods, nanoprecipitation is a fast and simple process, which does not require a pre-prepared polymer emulsion before the nanoparticle preparation. It produces a dispersion of nanoparticles by precipitation of preformed hydrophobic polymer solution. Under... 

Nanoprecipitation is one of the commonly used processing methods to produce polymeric nanoparticles. Since the method is efficient, economical, and accurate, nanoprecipitation is better than the other methods, such as dialysis, solvent evaporation, and salting-out. It is a technique used to produce nanoparticles in the form of nanocapsules, nanospheres, and polymersomes. Polymeric nanoparticles have gained the interest, because of their applications, such as drug delivery, targeting specific organs, and reducing the problems associated with conventional particles. Therefore, proficient methods like nanoprecipitation are necessary to produce nanoparticles in an efficient way for many applications. 

The procedure chosen for the preparation of lipid complexes of AmB was nanoprecipitation. This procedure has been developed in our laboratory for a number of years and can be applied to the formulation of a number of different colloidal systems liposomes, microemulsions, polymeric nanoparticles (nanospheres and nanocapsules), complexes, and pure drug particles (14-16). Briefly, the substances of interest are dissolved in a solvent A and this solution is poured into a nonsolvent B of the substance that is miscible with the solvent A. As the solvent diffuses, the dissolved material is stranded as small particles, typically 100 to 400 nm in diameter. The solvent is usually an alcohol, acetone, or tetrahydrofuran and the nonsolvent A is usually water or aqueous buffer, with or without a hydrophilic surfactant to improve colloid stability after formation. Solvent A can be removed by evaporation under vacuum, which can also be used to concentrate the suspension. The concentration of the substance of interest in the organic solvent and the proportions of the two solvents are the main parameters influencing the final size of the particles. For liposomes, this method is similar to the ethanol injection technique proposed by Batzii and Korn in 1973 (17), which is however limited to 40 mM of lipids in ethanol and 10% of ethanol in final aqueous suspension. 

This method, also known as the nanoprecipitation method, can be applied to numerous synthetic poly-mers. ° In general, the polymer is dissolved in acetone and the polymer solution is added into water. The acetone is then evaporated to complete the formation of the particles. Surface active agents are usually added to water to ensure the stability of the polymer particles. This easy technique of nanoparticle preparation was scaled up for large batch production. It leads to the formation of nanospheres. Nanocapsules can easily be prepared by the same method just by adding a small amount of an organic oil in the polymer solution.When the polymer solution is poured into the water phase, the oil is dispersed as tiny droplets in the solvent-non-solvent mixture and the polymer precipitates on the oil droplet surface. This method leads to the preparation of oil-containing nanocapsules... 

The presence of the surfactant SDS influences nanocapsule formation in two ways With increasing SDS cmicentration, the nanocapsules become smaller. At the same time, with decreasing size of the nanocapsule, the coverage of the nanoobjects (before evaporation of the solvent, the nanodroplets after the evaporatimi, the nanoparticles or nanocapsules) by SDS increases, leading to a decrease in the interfacial tension of droplel/water and copolymer/water. The interfacial tension between copolymer and water ( 0.035 N/m) without surfactant is considerably smaller than the interfacial tension between hexadecane and water ( 0.054 N/m). Thus, in the case of a low concentration of SDS and subsequent coverage of the nanoobjects by SDS, the interfacial tension of the copolymer/water interface is lower than that of the hexadecane/water interface therefore as the thermodynamically most stable structure, nanocapsules are expected to be formed (Fig. 54a). 

The preparation of nanoparticles by precipitation from an organic solution is well known from the preparation of polymeric nanocapsules and can also be used for the SLN production. The lipid, drug and the stabilizer(s) are dissolved in a water-miscible organic solvent (e.g. acetone, ethanol) or solvent mixture and this solution is dropped in the stirred aqueous phase that may contain a hydrophilic surfactant. Chen et al. firstly evaporated a part of the solvent mixture at elevated temperature before injection into the cooled aqueous phase under stirring. ... 

Figure 9.20 The data show that the inlet jet Reynolds number (Re ) is a good scale up criterion for geometrically similar scaled CIJ mixers CIJ-d2 data are also shown to evidence that a variation of the inlet tube/chamber diameter ratio may influence the final particle size. Both PEGylated copolymer nanospheres and nanocapsules are shown, evidencing different dependence on Re. quenched samples (quench ratio = 1) in the upper graph, non-quenched in the lower graph, measured after solvent (acetone) evaporation. Nanocapsules (containing Miglyol , MR=1.26) , scale down , reference (CIJ-dl) , scale up A, CIJ-d2. Polymer nanospheres , scale down O, reference (ClJ-dl) O, scale up , CIJ-d2.

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