Application of Nanoparticles as a Drug Delivery System

2. Preparation Of Nanoparticles

Polymer nanoparticles including nanospheres and nanocapsules (Figure 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 (Scheffel et al., 1972; Marty et al., 1978). 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 methylmethacrylate (Birrenbach, Speiser 1976; Kreuter, 1976). 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 synthetic polymers. Couvreur et al., proposed to make nanoparticles by polymerization of monomers from the family of alkylcyanoacrylates already used in vivo as surgical glue. They succeeded in making nanoparticles by polymerization of the monomers in oil-in-water type emulsions prepared with an acidified aqueous phase (Couvreur et al., 1979).

During the same period of time, Gurny et al., proposed a method based on the use of another biodegradable polymer consisting of poly(lactic acid) used as surgical sutures in humans (Gurny et al., 1981). In this method, nanoparticles were formed directly from the polymer. Based on these initial investigations, several groups improved and modified the original processes mainly by reducing the amount of surfactant and organic solvents. At that time, the methods developed were only able to produce nanospheres (Figure 1) (Legrand et. al. 1999). A breakthrough in the development of nanoparticles occurred in 1986 with the development of methods allowing the preparation of nanocapsules corresponding to particles displaying a core-shell structure with a liquid core surrounded by a polymer shell. From 1986, there was also an acceleration in the development of new methodologies for the preparation of all types of nanoparticles.