Polymeric Nanoparticle Preparation Methods

Polymeric nanoparticles can be formulated from either preformed polymers or monomers by a variety of methods. However, the most popular methods to prepare polymeric nanoparticles start from biocompatible preformed polymers (Hans and Lowman 2002).

8.1.1 Emulsification Solvent Evaporation Method

The polymer is dissolved in an organic solvent first, and then the drug is dissolved into the polymer solution to create a mixture of drugs dispersed in a polymer solution. The emulsion is prepared by adding water and a surfactant to the polymer solution. In many cases, the nanosized polymer droplets are induced by sonication or homogenization. The organic solvent is then evaporated and the nanoparticles are usually collected by centrifugation and lyophilization (Torche et al. 2000; Suh et al. 1998; Song et al. 1997; Cheng et al. 1998; Feng and Huang 2001). In this method, both water-soluble and water nonsoluble drugs can be incorporated into polymeric nanoparticles; however, hydrophilic drugs have traditionally showed a lower incorporating efficiency (Hans and Lowman 2002).

8.1.2 Emulsification-Diffusion Method

Here, the solvent is chosen as a partially water-soluble solvent (e.g., acetone). The polymer and drug are dissolved in the solvent and emulsified in the aqueous phase containing the stabilizer. The role of the stabilizer is to prevent emulsion droplets from aggregating. Then, water is added to the emulsion to allow for the diffusion of the solvent into the water. The solution is stirred, resulting in the precipitation of nanoparticles which can be collected by centrifugation (Kwon et al. 2001; Takeuchi et al. 2000). The problem with this method is that water-soluble drugs tend to leak out during the diffusion of the solvent.

8.1.3 Nanoprecipitation Method

The polymer and drugs are dissolved in acetone and added to a solution containing Pluronic F68, which is a difunctional block copolymer surfactant terminating in primary hydroxyl groups, a nonionic surfactant that is 100% active and relatively nontoxic. The acetone is then evaporated under reduced pressure and the nanopar-ticles remain in the suspension (Vergera et al. 1998).

8.1.4 Salting-out Process

Water-in-oil emulsion is formed containing the polymer, acetone, magnesium acetate tetrahydrate, stabilizer, and the drugs. Then, water is added until the volume is sufficient to allow for diffusion of the acetone into the water, which results in the formation of nanoparticles. The suspension is purified by cross-flow filtration and lyophilization (Leroux et al. 1996). One disadvantage to this procedure is its use of the salts that are incompatible with many bioactive compounds.

As mentioned, the above methods are the most popular techniques to prepare nanoparticles from a platform of biocompatible preformed polymers (such as poly (lactic-co-glycolic acid) (PLGA), poly(lactic acid), poly(hexadecylcyanoacrylate), etc.). However, biodegradable nanoparticles can also be made from monomer polymerization methods (Sakuma et al. 2001; Behan et al. 2001). Hydrophilic poly-saccharides (like chitosan (CS)) can also be used to make polymeric nanoparticles by the spontaneous ionic gelatin process (Vila et al. 2002; Janes et al. 2001). This technique is becoming attractive because it does not use harmful organic solvents and can formulate particles of small sizes and positive surface potentials.

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