INFLUENCE OF STABILIZING AGENTS AND PREPARATIVE VARIABLES ON THE FORMATION OF POLY(D,L-LACTIC ACID) NANOPARTICLES BY AN EMULSIFICATION-DIFFUSION TECHNIQUE

Poly(D,L-lactic acid) (PLA) nanoparticles were prepared by a modified emulsification-diffusion technique. The preparation method consisted o f emulsifying a solution of polymer in an aqueous solution of a stabil izing agent, previously saturated, followed by diluting the internal p hase with an excess of water. Propylene carbonate (PC) was used asa pa rtially water-miscible solvent, due to its ability to dissolve polymer s, its low toxicity and its ease of emulsification. PC allowed the obt ention of nanospheres in a reproducible and efficient way, using poly( vinyl alcohol) or poloxamer 188 as stabilizing agents. The possibility of using poloxamer 188 to produce PLA nanospheres is an interesting o ption because of its well known acceptability for parenteral administr ation. With other well accepted stabilizing agents such as polysorbate 80, gelatin, polyvinylpyrrolidone and dextran, it was not possible to obtain nanoparticles. The effectiveness of the stabilizing agents in the process was attributed to their ability to avoid coalescence durin g PC diffusion. The formation mechanism of nanoparticles can be explai ned by the large interfacial area resulting from emulsification and th e gradual reduction of the globule size due to solvent transfer and pr obably, to the interfacial turbulence generated during diffusion. A hi gher concentration of polymer was found to rapidly increase the size a nd polydispersity of nanoparticles. In contrast, an increase in stirri ng rate and concentration of stabilizer agent were found to reduce mod erately the size of the nanoparticles. Other process parameters such a s viscosity, pH of the external phase and internal/external phase rati o had limited influence on particle size.