Nanospheres preparation methods

One of the advantages of this type of nanospheres is that, owing to the amphiphilic nature of the block copolymers PEG-R and PEG -R, the use of other surfactants (not always biocompatible) can be avoided. This is not the case with PLA (Bazile et al, 1995) or PLGA (Gref et al, 1994) polymers, whatever the nanosphere preparation method. The use of surfactants such as poly(vinyl alcohol) (PVA) or Pluronic is necessary for the formation of PLA and PLGA nanoparticles, and thus additional washing steps are required to remove adsorbed surfactant. 

We can classify the preparation methods for the formation of nanospheres on the basis of the material used as shown in the Table 1. 

Most methods of nanosphere preparation described in the literature involve potentially toxic organic solvents, which are difficult to remove from the preparation media. Thus, methods using only aqueous media represent promising alternatives. Unfortunately, these techniques are not suitable for encapsulating large quantities of lipophilic molecules because of their poor solubility in water. 

Fig. 8. Comparison of the typical hydrodynamic radius distribution f(Rh) of the polystyrene nanospheres prepared microwave irradiation and conventional heating method. Reprinted from (1997) Macromolecules 30 6388 [42] with permission...

T Niwa, H Takeuchi, T Hino, N Kunou, Y Kawa-shima. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with d,l-lacti-de/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. J Control Rel 25 89-98, 1993. 

Both nanospheres and nanocapsules are prepared from either a polymerization reaction of dispersed monomers or from a solvent dispersion procedure using preformed polymers. In many instances, the latter procedure using preformed polymer is desirable, as potential reactions between drug and monomer are avoided and the potential toxicity of residual monomers, surfactant, and initiator is reduced [37], The final properties of nanoparticles, such as their size, morphology, drug loading, release characteristics, and biodisti-bution, are all influenced by the method of preparation [38],... 

This procedure is also referred to as the precipitation method and was first reported by Fessi et al. [105]. In this type of preparation, as shown in Figure 7, the polymer is dissolved in a water-miscible solvent and then poured under stirring into a nonsolvent, which is usually water. This leads to the polymer precipitating as nanospheres. Prior emulsification and inclusion of surfactants are not necessary. 

Figure 7. Preparation procedure for precipitating technique. Shown also is the schematic illustration of the diffusion stranding mechanism for nanosphere formation that occurs during the precipitation method.

Figure 8. Preparation mechanisms of PLGA nanospheres by the emulsion-phase separation method in an oil system.

Figure 6.4 The preparation of nanostructured materials in solution evolves from (a) the classic examples of suspension, dispersion, or emulsion polymerization, to the methods that include the covalent crosslinking of select domains within supramolecular polymer assemblies (b) core crosslinking of polymer micelles (c) shell crosslinking of polymer micelles (SCKs) (d) nanocages from core-eroded SCKs (e) shaved hollow nanospheres from outer shell/core-eroded vesicles.

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. 

The drug can be dissolved, entrapped, encapsulated, or attached to a nanoparticle matrix, and depending upon the method of preparation, nanoparticles, nanospheres, and nanocapsules can be obtained (Soppimath et al. 2001). 

Lemos-Senna, E., Wouessidjewe, D., Lesieur, S., and Duchene, D. (1998), Preparation of amphiphilic cyclodextrin nanospheres using the emulsion solvent evaporation method, influence of the surfactant on preparation and hydrophobic drug loading, Int. J. Pharm., 170,119-128. 

Common methods for the fabrication of metallic nanoparticle arrays are electron beam lithography, photolithography, laser ablation, colloidal synthesis, electrodeposition and, in recent time, nanosphere lithography for which a monodisperse nanosphere template acts as deposition mask. A review on advances in preparation of nanomaterials with localized plasmon resonance is given in [15]. 

Polymer nanoparticles including nanospheres and nanocapsules (Fig. 1) can be prepared according to numerous methods that have been developed over the last 30 years. The development of these methods occurred in several steps. Historically, the first nanoparticles proposed as carriers for therapeutic applications were made of gelatin and cross-linked albumin. Then, to avoid the use of proteins that may stimulate the immune system and to limit the toxicity of the cross-linking agents, nanoparticles made from synthetic polymers were developed. At first, the nanoparticles were made by emulsion polymerization of acrylamide and by dispersion polymerization of methylmethacry-late.f These nanoparticles were proposed as adjuvants for vaccines. However, since they were made of non-biodegradable polymers, these nanoparticles were rapidly substituted by particles made of biodegradable... 

The poly(alkylcyanoacrylate) nanospheres, widely used as drug carriers, are prepared by emulsion polymerization according to a method initially introduced by Couvreur et al. The monomers (isobutylcyano-acrylate, isohexylcyanoacrylate, n-butylcyanoacrylate) are dispersed in a continuous acidified aqueous phase under magnetic agitation. The anionic polymerization... 

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