ABSTRACT
Nanoparticles are submicronic structures (diameter below 1 /xm) made with polymers. They are mainly developed as drug delivery systems as an alternative to liposome technology in order to overcome the problems related to the stability of these vesicles in biological fluids and during storage (1). Nanoparticles were first designed using albumin (2) and nonbiodegradable synthetic polymers such as polyacrylamide and poly (methyl methacrylate) (3,4). The risk of chronic tox icity due to the intracellular and/or tissue overloading of nondegradable polymers was soon considered as a major limitation for the systemic administration in man of polyacrylamide and poly (methyl methacrylate) nanoparticles. With the administration of protein-based material, the major concern was the possible antigenic response. As a consequence, the type of nanoparticle that received much attention was designed with synthetic biodegradable polymers including polyalkylcyanoacrylate, poly(lactic-co-glycolic acid), and polyanhydride (5-11). The therapeu tic potential of these biodegradable colloidal systems was investigated for various applications (10-19). Despite the very interesting results reported in the literature, these systems may also be concerned with toxicological problems (20,21). In addition, they often present limitations for the administration of hydrophilic molecules such as peptides, proteins, and nucleic acids (oligonucleotides and genes) which are recognized to have great potential in therapeutics. These limitations are mainly because the polymers forming these nanoparticles are mostly hydropho bic, whereas proteins, peptides, and nucleic acids are hydrophilic. This leads to difficulties for the drug to be efficiently encapsulated and protected against enzymatic degradation (16,22-24). Therefore, the preparation of nanoparticles using more hydrophilic and naturally occurring ma terials has been explored (25-29).
